Self Gravity: The Major Investigation Gap in Life … · How to cite the article:Bhattacharjee IR. Self Gravity: The Major Investigation Gap in Life Science (Part I). ... The Major

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Self Gravity: The Major Investigation Gap in LifeScience (Part I)Corresponding Author:Dr. Iresh R Bhattacharjee,Principal Scientist, Institute for Instrinsic Gravitation Biology (i3GB) {Assam Agricultural University}, 84,GMCHRoad, Anandanagar, Dispur, Guwahati-781 005 India {C/O L.Dr.G.C.Bhattacharjee, Longai Road,Karimganj-788712, India}, 781005 - India

Submitting Author:Dr. Iresh R Bhattacharjee,Principal Scientist, Institute for Instrinsic Gravitation Biology (i3GB) {Assam Agricultural University}, 84, GMCHRoad, Anandanagar, Dispur, Guwahati (C/O L Dr G C Bhattacharjee, Longai Road, Karimganj-788712, Assam,India), 781005 - India

Article ID: WMC004279

Article Type: My opinion

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Keywords:Gravity, gravitational potential energy, metabolic energy, buoyant force, self organization,astrophysics

How to cite the article:Bhattacharjee IR. Self Gravity: The Major Investigation Gap in Life Science (Part I).WebmedCentral BIOPHYSICS 2013;4(6):WMC004279

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Self Gravity: The Major Investigation Gap in LifeScience (Part I)Author(s): Bhattacharjee IR

Abstract

Potential binding energy of self gravity acts universallyon mass which is being ignored in living world atmesoscopic length scale without tangible reason. It isconceptualized that biomass accumulated throughphotosynthesis and other build-up mechanism withinvolume of secluded structure serve as foundation.Within membrane bound volume of mass, build up andbreak down mechanism through anabolism andcatabolism of metabolic energy causes a change inthe amount of mass per unit volume at particularinstant leading to contraction out of gravitationalpotential energy and relaxation due to inertia pluskinetic energy of metabolic activity, develops pressurewith gain or release of temperature. Backgroundtension within volume causes mass to moveasynchronously at low frequencies and continues tofunction as ‘life’. Kinetic energy producing organelles(mitochondria, chloroplast) remain away from centralload. Self gravity attracts denser materials to its coreleading to sorting and self assembling of massaccording to density-gradient of macromolecules.Nucleic acid having higher density finds place as ‘core’,medium denser protein in intermediate and leastdense fat in the periphery. Metabolically inertinfrastructure or buoyant force of fluids secludes selfgravitating body from external stronger gravitationalfield and helps to maintain self gravity’s free fallcondition. With collapse of equilibrium betweencontraction and relaxation of self gravity, strongerforce of extrinsic gravity makes living mass inertnon-living.

Under the principle of abductive reasoning throughsuccessive approximation on sporadic set ofobservations, roles of self gravity on identicalastrophysical principles of larger mass have beenconceptualized on some evidences detailed in Part Iand II of the article. Various interior dynamics includingself organization of macromolecules, proteinconformation, movement of human thoracic diaphragm,formation of logarithmic spiral in nature werediscussed in the light of potential energy of self gravityand kinetic energy of metabolic energy.

Content

INTRODUCTION

Ι. PHYSICAL PROPERTY OF SELF GRAVITY

1. Self organization- intrinsic property of self gravity2. How self-gravity could be strong at miniature scale?3. How binding action of self gravity could be areckonable force in biomass?

ΙΙ. SECLUSION MAINTAINS SELF GRAVITY’S FREE FALL CONDITION

4. Mechanism of seclusion from extrinsic gravity5. Relative three tier reference frame6. Buoyant like force maintain self gravity’s free fallcondition7. Reduced fluid level stop metabolism8. Neutral buoyancy can apparently reduce the weightof living mass9. Nanometer level free fall acceleration forfemtometer size macromolecules10. Buffering action through repelling electrostaticforce11. Metabolically inert infrastructure (MII) as cell’sseclusion environment12. Behavior of living mass under different types ofmedium13. Importance of medium vis-à-vis unperturbed selfgravity

ΙΙΙ. METABOLIC ENERGY AND SELF GRAVITY

14. Whether gravitational anchor is a criterion formanifestation as living?15. Energy producing organelles or sites located awayfrom the centre16. Some anomalous hypothecations in health science17. Body Mass Index (BMI) 18. Body Surface Area (BSA) 19. Basal Metabolic Rate (BMR) ΙV. CENTRE OF SELF GRAVITY

20. Why central position is vital?21. Why nucleoid, nucleolis or nucleus tend to remain



in central position?22. Generation of ‘muscle tone’ remains elusive inhuman physiology23. ‘Build-up’ & ‘break-down’ mechanisms in livingmass24. Spectacular action of self gravity in muscle tonewhile living and not when dead25. There is no complete loss of tone during paralysis26. Tone is lost after death during pallor mortis and notwhile living 27. Intrinsic muscle tone is constantly maintainedwhen living but loose after death 28. Edema occurs in lowers or dependant parts of thebody after death29. Intuitive model on generation of ‘background tone’30. Abundance of logarithmic spiral in nature vis-à-visself gravitating phenomena31. Human average body frequency 32. Body cools down on death after loss ofcontraction-relaxation of self gravity 33. Which force regulates stretching and relaxationduring oesophageal peristalsis?34. What causes channel narrowed or dilated duringtrafficking?35. Why nuclear-cytoplasmic ratio is important forhealth?36. Matching inward wall pressure in cellular activityvis-à-vis self gravity37. Mechanical loads and centrosome - microtubuleorganization38. Inner cell mass (ICM) influences potency in stemcells? 39. Metacenter and floating principle 40. Neucleus and neucleolus- ‘core’ segment of theself gravitating interior41. Change in concentric to eccentric nucleus underneutral buoyant condition42. Prototype of interior dynamics of self gravitatingbiomass

V. GENERAL PROPERTY OF SELF GRAVITY

43. Self organization due to self gravity44. Formation of twin centre of mass on decrease inmutual attraction 45. Self gravity dictates self organization ofmacromolecules in living cell46. Globular protein form and self gravity47. Native conformation, denaturation & renaturationof protein and self gravity48. Some exceptions to general rule49. Spheroids fibrous protein and self gravity50. Protein folding problem and topological property51. Proteins fold on funnel-shaped energy landscapes

VI. REFERENCES (INCLUDING TABLES &ILLUSTRATIONS)

Introduction

The trend among biologists is to describe anyunexplained phenomenon as the gift of nature. This isirritating for any sensible person. Nature cannot act inself styled manner. It must obey certain definedphysical rules. Hence such outlook needs appropriatecorrection. We must find continuity in the formation ofthe universe, the galaxy, the solar system to a tinycreature up to smallest bacteria or plasmid. Whatcould be the force or factor that keeps such continuityfrom macro to meso or up to micro length scale? Forinstance, it is said that bilateral symmetry in animals isdue to necessity to cope up with the environment.Personally you or I feel the necessity of having ‘thirdhand’ or ‘third eye’ in the backside to ward off manydisadvantages we feel daily. The phenomena ofbilateral symmetry are often described as ‘natural’.Why nature should act spontaneously? Similarly, say,muscle tone or background tensions remain elusive inhuman physiology. Tone works 24 hours a day. Whenmuscles are at rest, a certain amount of tautnessusually remains. Contraction in healthy human muscletone i s m in imum 5 pu lses pe r second .Electromyograph evidence shows that the muscle iselectrically silent. Low frequency tone cannot bedetected by electromyography. Some quartersuspects that muscle tissue itself has an intrinsicelasticity. But if that were true, we would have to befighting against that elasticity every time we used askeletal muscle. Again all muscle contraction begins inthe muscle core. Even in flat muscles contractionstarts in the central plane, and then works its way out.Why muscle contraction begins in the muscle core?Similarly many other questions in life science are stillnot appropriately answered or if answered, these aredifficult to digest in absence of supporting reasoning.In the same way, for instance, over the issue of ‘selforganization’ in the cell, life science is passing througha major crisis. A living cell is not an aggregate ofmolecules but an organized pattern, structured inspace and in time. Harold M Franklin1 in 2005 madeextensive reviews on the spatial organization of cells,including the arrangement of cytoplasmic constituentsand the cells' global form, which is not explicitlyspelled out in the genome. Genes specify only theprimary sequences of macromolecules, portions ofwhich are indeed relevant to the localization of those



molecules in space. But cell architecture, for the mostpart, arises epigenetically. What could be the invisibleepigenetic mechanism that could be the driving forceand bu i l ds up o rgan ic comp lex i t y i n amembrane-bound, structured setting and lead tospontaneous self-emergence of spatially organizedsystems from where molecules come to life?

Working on range of paradoxes in biology, on criticallyexamining various reported works on these aspects,on undertaking strategic experimentations andobserving on diverse living organisms randomly but ina purposeful meticulous way for last 40 years from abinitio stage to intermediate and final status, duringintact state (in vivo), under removed condition (ex vivo)as well as in vitro culture of various living organismsand on carefully avoiding over-interpretation that maynot lead to erroneous conclusions, I came to theapproximation that presence of intrinsic gravity or inother words, self gravity, an invisible binding force thatholds the body structures in place or is responsibleprimarily for ‘self organization’, building up of lowfrequency but steady muscle tone is difficult to ignore.Gravity is the building block of the universe. The realityof the cellular interior might be determined by theequilibrium between ‘build up’ and ‘break down’ ofmass leading to its gain or loss. A reversiblemechanism between kinetic and potential gravitationalenergy due to variation in instant mass might createinternal pressure. Such internal pressure might workagainst self gravitational compression. Thesurrounding hydrostatic pressure might help to createself gravitating environment around a living mass. This is also what is going on in the interior of theuniverse, in the galaxy, in the star, the sun, the planetand the moon. The materials may differ but all worksmight be on the same principle of equilibrium betweeninternal pressure and gravitational pressure. Theequilibrium or balance might be the law of life fromuniverse to living bodies.

As per concept of molecular biology, DNA sequencesare transcribed into RNA and then translated intoamino acid chains; the latter fold spontaneously intofunctional proteins. But genesis of spatial architecture,including how molecules find their proper location incell space, the origins of supramolecular order, cellmorphology are not yet satisfactorily answered. HaroldM Franklin1 therefore concluded that “We urgentlyneed a plausible and experimentally fertile hypothesisthat starts with a driving force and builds up organiccomplexity in a membrane-bound, structured setting.No satisfying hypothesis of this kind is presently on thebooks, and in its absence holistic explorers of deeptime have been unable to initiate a research tradition

that can thrive in today's intellectual and fiscal climate.But I have no doubt that this is the way to go; for onlythrough the emergence of spatially organized systemscan molecules come to life”. From all such gap areasof investigations, the present study was undertaken todefine the role of self gravity in living mass.

Physical Property of SelfGravity

1. Self organization- intrinsic property of selfgravity

To understand nature of self gravity, Prof. J.V.Narlikar2, eminent astrophysicist, used an imaginaryepisode from the life of Aladdin. The Arabian Nightsstory of Aladdin and the magic lamp ends with Aladdinliving “happily even after” with his princess and hismagic lamp. But one hot summer’s day, Aladdin, whileon a tour of the Arabian Desert suffered sunstroke. Hesummoned the genie of the magic lamp and issuedcommand “Take the Sun apart and distribute its bitsand pieces far and wide so that it is completelydestroyed”. Genie started chipping off bits and piecesfrom the surface of the Sun. He has to work againstthe force of gravity ( ), where G is the gravitationalconstant; M is mass and R is radius). Aladdin began tohave a second thought. He realized how essential theSun was to the inhabitants of the Earth, includinghimself. So, while the genie was in the process ofcompleting the job, Aladdin issued his next command:“Put all the bits of the Sun back together”. The poorgenie went back to execute the command. However,this time, to bring all the constituents of the Suntogether, the genie no longer had to work against thegravity. In fact, while the genie had been temporarilycalled away by Aladdin to issue his second command,the bits and pieces left in space by the genie hadalready began to fall back together. Self gravity, whichhad been a opposing force for the first job, had nowturned into an ally. And to put the Sun back together,the genie had to do no work. Instead, the amount ofwork, which the genie had earlier expended on the firstjob against the force of self gravity, would now bedone by the force of self gravity to put the Sun backtogether (illustration 1). So from the imaginary storyabove it is clear that the self gravity is the naturalinward compressive force having potential energy forwhich genie had nothing to do to put sun in position.We will demonstrate how self gravity would be thebinding force not only at organism level but even atmacromolecular level.



2. How self-gravity could be strong at miniaturescale?

Gravity is the invisible building block of the universe.Among the basic forces (nuclear, electro-magnetic &gravity), gravity acts on ‘mass as action at-a-distance’.Living organism without "mass" cannot be imagined.So effect of gravity in living mass cannot be ignored.Biology starts in the part ic le hierarchy innon-Newtonian state, with accumulation of‘macromolecular mass’ at organelles or cell level3,4,9 (Illustration 2). The particle hierarchy shows sub-atom,atom, molecule, compound, organelles, cells, tissue,organ, organ system, and organism. Here we are tocompare vital question on presence of competitiveforces like electromagnetic, nuclear and elastic forcesthat could act as binding force at miniature scale. Bothgravity and electromagnetism obey the inverse-squarelaw, i.e. their strength declines by the square of thedistance between interacting systems. In otherrespects, however, they seem to be very different. Forinstance, the gravitational force between two electronsis 42 orders of magnitude (1042) weaker than theirelectrical repulsion. The reason electromagnetic forcesdo not completely overwhelm gravity in the worldaround us is that most things are composed of anequal amount of positive and negative electric chargeswhose forces cancel each other out. Whereas electricand magnetic forces are clearly bipolar, gravity isgenerally assumed to be always attractive so that noanalogous cancellations occur. Gravity works onmass without any time frame, as if relatively constantlike physical structure of a house. Electromagneticforce works on ‘charges’ in time bound manner, as if arelatively variable like an electric bulb based on off andon switch. All time supremacy of self gravity on massas potential energy therefore cannot be ignored.

On the other hand, theoretical calculation shows thatexertion of gravitational forces which follows inversesquare law gets increased from 0.0007 to 6.6726dynes when quantity in two masses increase from 10-4

to 10-2 grams under same separation distance of 10-6

centimeter (Illustration 3 Table 1). Similarly whenseparation distance is decreased from 10-6 centimeterto 10-10centimeter for the same two masses of 10-4

grams each, the gravitational force is increased from0.0007 to 66,726 dyne (Illustration 4 Table 2).

Sizes of some biomass are mentioned below for readyreference. A prokaryotic cell of E.coli is about 2 µm or2x10-6 m long, 1 µm wide, diameter 0.8 µm, wet weight1x10-15 kg or 1x10-12 g, dry weight 3.0x10-16 kg or3.0x10-13 g. Viruses range in between 30 to 300 nm or300 to 3000 A0 in size. The protein comprising a prionhas a molecular weight between 50,000 to 100,000,

corresponding to a particle size that is 100 timessmaller than the smallest virus. Micoplasmas range insize (diameter) from 0.25 to 0.1 µm. Even with suchminiature size, force of gravity cannot become extinct.With higher density of mass, gravitational potentialenergy gets increase. Interestingly living matter, unlikenon-living, has got two categories of metabolism,anabolism that builds up mass and catabolism thatbreaks down mass of carbohydrates. Gravitationalbinding energy works on mass as potential energywhereas kinetic energy is created from such mass.The total human body content of ATP is about 50grams, which must be constantly recycled every day.The average daily intake of 2,500 food caloriestranslates into a turnover of a whopping 180 kg of ATP.With breakdown of mass through catabolism, therewould be a variation in the kinetic energy at an instant.It is a continuous process. When contacting surfacesmove relative to each other due to potential and kineticenergy, a pressure is developed out of friction withrising of temperature. Researchers have found thatbasal metabolic rate (BMR) or amount of energyexpended for an organism is proportional to Mass 2/3 to¾. There is a strong relation of mass with gravitationalenergy and metabolic rate in living organism. This is amajor gap area of investigation in life science tocorrelate potential gravitational energy and metabolickinetic energy from the same amount of mass.

3. How binding action of self gravity could be areckonable force in biomass?

Gravity is customarily considered as long distanceforce acting on massive body. But in fact, biologystarts in non-Newtonian state as soft condensedmatter in which the viscosity changes with the appliedshear stress. Unlike fluid (say, water) which couldreturn back to its original position after withdrawal ofstress, soft matter displays a range of fascinatinggeneric properties such as ability to ‘self assemble’into complex structures, a large number of internaldegrees of freedom, weak interactions betweenstructural elements, and a large thermal fluctuations atroom temperature, a wide variety of forms, sensitivityof equilibrium structures under metastable states toexternal conditions. The Newton’s inverse-square lawwould be valid if there is no additional dimension.However, if there are two additional dimensions, thedependence of the gravitational force would changefrom 1/r2 to 1/r4, or the gravitational potential couldtake the following form (Illustration 49 Equation 1 and2):

If dividing by 1/r2 is a small number, dividing by 1/r4

(twice of 1/r2) can make the correspondinggravitational force much stronger5,6.



On the other hand, gravitational binding energy of anobject consists of the amount of energy required topull all of the matters apart including amount of energythat is liberated in the form of rising temperatureduring the accretion of matters. The gravitationalbinding energy of a system is equal to the negative ofthe total gravitational potential energy, considering thesystem as a set of smal l part ic les. For aspherical mass of uniform density, the gravitationalbinding energy U is given by the formula7,8 (Illustration49 Equation 3):

where G is the gravitational constant, M is the mass ofthe sphere, and r is its radius. But radial densitygradients (ρ) of biological mass are not uniform.Normally there is lower density at the surfaces andcomparatively higher density in the inner partsincluding compressed cores or nucleus, which we willmention subsequently. This needs to be evaluatedwith appropriate data. Therefore ignoring intrinsicgravity in living organism, as negligible force, is difficultunder the present scenario. Gravity is not an instantforce like others. Its manifestation is visible only at thelater stage as an everlasting force.

Seclusion Maintains SelfGravity Free fall Condition

4. Mechanism of seclusion from extrinsic gravity

Arguments came from physicists that stronger earth'sgravity would swamp the intrinsic gravity of smallbiomass. But moon, being self gravitating body couldretain its identity on seclusion even being swamped bythe gravitational field of the earth, solar system or theuniverse. On close examination, clue can be found onseclusion for intrinsic gravity from extrinsic gravity. Anegg floats on saline water, on working against earth'sgravity, due to buoyant force (Illustration 5a).Buoyancy acts against the force of gravity and somakes objects seem lighter with respect to gravity. Torepresent this effect, which is important forsedimentation, it is common to define a buoyant massmb that represents the effective mass of the object withrespect to gravity (Illustration 49 Equation 4)

where mobject is the true (vacuum) mass of the object,whereas ρobject and ρfluid are the average densities ofthe object and the surrounding fluid, respectively. Thus,if the two densities are equal, ρobject = ρfluid, the objectappears to be weightless. If the fluid density is greaterthan the average density of the object, the object floats;if less, the object sinks. Various ionic fluids includingamniotic fluid secludes macromolecules or fetusesfrom earth’s gravity9,10,11 (Illustration 5b,5c). Fetuses

develop on seclusion in near-weightless environmentof mothers' wombs. During the last trimester, it turnsupside-down with head-lower condition.

5. Relative three tier reference frame

Spaargaren (1994) coined the term ‘metabolically inertinfrastructure’ (MII) 12 that consists of total body mass(body water, dissolved substances, mineral andorganic deposits) and serves as storage of nutrients,transport and distribution of these materials. To actindependently as living body, we propose that MIIprovide structural support for seclusion to themacromolecules or organisms with density-gradientbuoyant force against extrinsic gravitational attractionfor the biological mass.

Let self-gravitating biomass/ embryo, being poweredby metabolic energy (ME) be in the acceleratedreference frame, manifesting its physiological andgenetic functionality. ‘Metabolically InertInfrastructure (MII)’ placed in the co-movingnon-accelerated reference frame that are relativelystationary or at constant velocity, or non-aligned oracting in opposite direction of the energizedaccelerated self gravitating biomass or of the steadystate supporting inertial reference frame at thespecific point of time13,14,15 (Illustration 6) .

The situation is similar to children playing ball within acompartment of a running train. Here ball is in theaccelerated reference frame and compartment is inthe non-accelerated reference frame which is pivotedthrough wheels over inertial reference frame of theground earth (Illustration 7a, b). While playing, childrencannot distinguish whether they are playing in therunning compartment of train or in the stationaryground. In a moving but non-accelerating frame, theball behaves normally because the train and itscontents continue to move at a constant velocity.Before being dropped, the ball was traveling with thetrain at the same speed, and the ball's inertia ensuredthat it continued to move in the same speed anddirection as the train, even while dropping. In fact it isinertia which ensured that, not its mass. Therefore if agiven mass does not have the opportunity to interactwith the surrounding forces, it would continue to actindependently. The manifestation of various biologicalphenomena can be considered on the ‘principle ofequivalence’16. Gravitational force field is a central field;the gravitational forces are directed toward the centreof the gravitating mass. These forces decrease inproportion to the square of the distance. Therefore selfgravitating tiny biological mass under seclusion ornear weightless condition can act in independentmanner on the ‘principle of equivalence’ of larger mass.



6. Buoyant like force maintain self gravity’s freefall condition

We consider self gravity, central attracting force actingon mass under free fall condition. A membrane boundliving cell has three-dimensional region composed ofcytoplasmic matrix and other organelles. Underhydro-gravitational suspension, pressure gradient inthe ?uid is not uni-directional. Archimedes principleestimate buoyancy on the basis of density of the solidand the density of the ?uid and is valid only when thepressure gradient in the ?uid is uni-directional and canbe reduced to the constant of the form ∇ p = ρg, whereρ is the average density of the ?uid displaced by thesubmerged object and g is the gravity accelerationvector in the direction of the free fall of the object17,18.Only then the buoyancy force F becomes equal andopposite to the weight of the displaced ?uid W = ρgV.For a comparatively semi-solid macromoleculessurrounded by near spherically symmetric pressuregradients (such as a cellular nucleus suspended incellular interior) the estimation of the buoyancy forcemust include explicit integration of all pressure forcesthat act on the entire submerged surface of that object.

The divergence theorem (also called Gauss's theorem) 19

states that the total expansion of the fluid or gas insidesome three-dimensional region W equals the total fluxof the fluid or gas out of the boundary of W. In livingcells, the definition of the divergence therefore followsnaturally by noting that, in the absence of creation ordestruction of matter, the density within a region ofspace can change only by having it flow into or out ofthe region. By measuring the net flux of contentpassing through a surface surrounding the region ofspace, it is therefore immediately possible to say howthe density of the interior has changed. This propertyis fundamental in physics, where it goes by the name"principle of continuity"20. We propose that in biology,especially in living cell, such principles of continuitymay also operate. Divergences at a given pointdescribes the strength of the source or sink in the flowof fluid or gas representing expansion (positive) orcompression (negative) of the vector field. Integratingthe field's divergence over the interior of the regionshould equal the integral of the vector field over theregion's boundary. For near spherically symmetricpressure gradients (such as a cellular nucleussuspended in cellular interior) the estimation of thebuoyancy force must include explicit integration of allpressure forces that act on the entire submergedsurface of that object. We will discuss the issue indetails subsequently.

As per general model detailing concept of selfgravitation bio, every living cell is compressed by

invisible force of self gravity. As stated above, inbiological particle hierarchy (atoms, molecules,compounds, organelles, cell, tissues, organs, organssystem, organism), attractive central force of selfgravity becomes prominent at the level of organellesover other basic forces (viz. electromagnetic andnuclear forces) while on seclusion. In general relativity,gravity is not regarded as a true force, but just as themanifestation of space-time’s geometry on themovement of matter and energy. In cosmology, λ(lambda - the cosmological constant) is frequentlyreferred to as a sort of "negative gravity"21: instead ofattractive it's repulsive, and instead of getting weakerwith distance it gets stronger. However we are notgoing details of controversy over the validity of suchgravity.

7. Reduced fluid level stop metabolism

The cytosol or intracellular fluid (or cytoplasmic matrix)is the liquid found inside cells. The entire contents of aeukaryotic cell, minus the contents of the cell nucleus,are referred to as the cytoplasm. Most of the cytosol iswater, which makes up about 70% of the total volumeof a typical cell 20. In eukaryotes this liquid is separatedby cell membranes from the contents of the organellessuspended in the cytosol, such as the mitochondrialmatrix inside the mitochondrion. The entire contents ofa eukaryotic cell, minus the contents of the cellnucleus, are referred to as the cytoplasm. Inprokaryotes, most of the chemical reactions ofmetabolism take place in the cytosol, while a few takeplace in membranes or in the periplasmic space. Ineukaryotes, while many metabolic pathways still occurin the cytosol, others are contained within organelles. The cytosol has no single function and is instead thesite of multiple cell processes. Studies in the brineshrimp (Illustration 8) have examined how wateraffects cell functions. It was found that reducing theamount of water in a cell below 80% of the normallevel inhibits metabolism, with this decreasingprogressively as the cell dries out and all metabolismhalting at a water level about 30% of normal23. Withinadequate depth of supporting fluids, macromolecularmass in the interior lost their gravitational seclusionidentity. Kinetic energy of metabolism failed toovertake potential gravitational energy.

Why depth of fluid (below 80% of the normal) isimportant? Density (d) is defined as the ratio of anobject's mass (m) to its volume (v): d= m/v. Thespecific gravity of a substance is defined as the ratio ofthe density of the substance to the density of water (1gram/cm3). This ratio is a convenient physical propertysince it has no units and is therefore independent ofthe system of measure used to determine it. The



Pascal’s law24, 25 invites the presence of entity of twobodies; first one is to dip on the other and pressure byit is to be applied to the enclosed liquid to express intransmitting equally to every part of the liquid (Illustration 9). Effect of change in height in the cytosolor fluid column within living architecture, as in Pascal’slaw can be considered as gap areas of investigation interms of potential and kinetic energy of gravitation andmetabolism respectively. Is it what Harold M Franklin1

prompted to say that “of cellular morphogenesis … weknow much but understand little.”

8. Neutral buoyancy can apparently reduce theweight of living mass

Neutral buoyancy is said to be a condition in which aphysical body's density is equal to the density of thefluid in which it is immersed. This offsets the force ofextrinsic gravity that would otherwise cause the objectto sink. An object that has neutral buoyancy willneither sink nor rise. The actual mass of the humanbrain is about 1400 grams; however, the net weight ofthe brain suspended in the cerebrospinal fluid (CSF) isequivalent to a mass of 25 grams18 i.e. what is 56 gmin human body will appear to be 1 gram only underneutral buoyant condition of the brain. The brain existsin neutral buoyancy, which allows the brain to maintainits density without being impaired by its own weight,which would cut off blood supply and kill neurons inthe lower sections without cerebrospinal fluid (CSF)26.

We know what is 6 kg on earth is 1 kg weight at moon.When a person arrives at moon, he will be acting asper external gravitational force of the moon and not asper that of earth. Accordingly a person when reachesmoon feels lighter. A normal weight of a human childat birth is say 3200 gm on earth but at moon its weightwould be 531 gm.

Amniotic fluid index (AFI) is a rough estimate of theamount of amniotic fluid27 and is an index for the fetalwell-being. It is a part of the biophysical profile (Illustration 10). AFI is the score (expressed in cm)given to the amount of amniotic fluid seen on pregnantuterus and calculated by a ultrasonograph Todetermine the AFI, doctors may use a four-quadranttechnique 28, 29, when the deepest, unobstructed,vertical length of each pocket of fluid is measured ineach quadrant and then added up to the others, or theso called "single deepest pocket" technique30. Thelinea nigra is used to divide the uterus into right andleft halves. The umbilicus serves as the dividing pointfor the upper and lower halves. The transducer is keptparallel to the patient’s longitudinal axis andperpendicular to the floor. The deepest, unobstructed,vertical pocket of fluid is measured in each quadrant incentimeters 31. The four pocket measurements are

then added to calculate the AFI. An AFI between 8-18is considered normal. Median AFI level isapproximately 14 from week 20 to week 35, when theamniotic fluid begins to reduce in preparation for birth.An AFI < 5-6 is considered as oligohydramnios. Theexact number can vary by gestational age. The fifthpercentile for gestational age is sometimes used as acutoff value. An AFI > 20-24 is consideredas polyhydramnios. What is the inner purpose of AFI?

9. Nanometer level free fall acceleration forfemtometer size macromolecules

Under secluded gravitating environment, nanometerlevel free fall acceleration would be a tremendousforce for femtometer size macromolecules. Let usinterpolate and visualize the phenomena with somesuperimposed data. Literature on neutral buoyantforce of amniotic fluid and utero as well as ex uteromeasurements is scanty. Let us concentrate ourattention to the works of Junwu Mu et al32 who made invivo quantification of embryonic and placental growthduring gestation in mice using micro-ultrasound andpair-wise comparisons of in utero and ex uteromeasurements. They reported that when gestationalage of mice reaches 16.5 days, the non-invasivepredictive body weight remains to 0.792 gm in average.The crown-rump length (CRL) and abdominalcircumference (AC) was reported to be the function ofgestation age (Illustration 11). The CRL and ACremain to be 16.22 mm and 23.4 mm respectively atthat growth stage of mice. The average radius of thefetus can thus be considered to be roughly 9.9 mm.

Let us extend theoretically the fetal weight floatingover amniotic fluid on the same principle of loss ofbrain weight in cerebrospinal fluid. Ignoring differencein the value of neutral buoyancy in cerebrospinal andamniotic fluids, due to differential presence of salt andother matters, the neutral buoyant weight of miceembryo of 0.792 gm would appear to be 0.014gm. The acceleration due to gravity on earth is about 9.8m/s2, whereas at moon it is 1.62 m/s2. However, if wecalculate acceleration due to (self) gravity in 0.792gram at 16 days of gestational age of mice with radius9.9 mm, separated by neutral buoyant force, asprovided by Junwu Mu et al[27], using standard formulag(s)= GM/R2, it comes to be about 5x10-9 m/s2. That isfree fall acceleration to the tune of 5 nanometer persecond square in a massive body of the planet may benegligible, but in an isolated living mass of the size 9.9femtometer (9.9x10-12 meter), acceleration of 5 nm/s2

is quite a significant force.

Soccer is being played by all ages. Age wise, playingstandard, materials, circumference or weight of ballmay differ. For youth/adult, ball may be of leather



having 70 cm circumference and 450 gram weight. Forhigh school level students, circumference and weightof the ball may be reduced to 62 cm and 396 gramrespectively. For kids, weight could be less than 100grams. Everyone will play as per individual capabilities(Illustration 12). Similarly action of self gravity on earthcan result an apple to fall on earth, or that of moon cancause a person to move easily when at moon.Similarly free fall acceleration at nanometer levelwould be tremendous for protein, fat or anymacromolecule of femtometer size and should not beoverlooked in tiny fetal body within its self gravitatingmass. As such importance of operation of neutralbuoyancy at cytosol or intracellular fluid (orcytoplasmic matrix) at cell level or amniotic fluid atmammalian level as mechanism for buffering pad tomaintain self gravity’s free fall condition is difficult toignore.

10. Buffering action through repell ingelectrostatic force

Lipid bilayer is a universal component of all cellmembranes (earlier it was designated as cell surfacecoat). The structure is called a "lipid bilayer" because itcomposed of two layers of fatty acids organized in twosheets. The lipid bilayer is typically about fivenanometers to ten nanometers thick and surrounds allcells providing the cell membrane structure. With thehydrophobic tails of each individual sheet interactingwith one another, a hydrophobic interior is formed andthis acts as a permeability barrier 33. The hydrophilichead groups interact with the aqueous medium onboth sides of the bilayer. The two opposing sheets arealso known as leaflets. Due to electrostatic force,these double bonds inhibit "packing" of the molecules(in solids). Therefore in limited manner, the lipidbilayer may act as cushion or buffering pad forseparation between gravity barriers of two gravitatingbodies (self gravity and extrinsic gravity) undersimultaneous operation and thereby possibly providesopportunity for secluded environment towardsunhindered action of the self gravity.

11. Metabolically inert infrastructure (MII) as cell’sseclusion environment

Cytoplasm is composed mainly of water and alsocontains enzymes, salts, organelles, and variousorganic molecules. As stated earlier Spaargaren (1994)coined the term ‘metabolically inert infrastructure’ (MII)12

to describe liquids in the cell. In unicellular organisms,cell’s environment- viz. a substratum beneath it, aliquid medium around it and neighboring cells beside it;whereas in multicellular organisms, aggregation ofcells and tissues with sufficient intra and extra-cellularmatrix in totality affect ‘life’, due to co-moving

non-accelerated position of the metabolically inertinfrastructure (MII) that are relatively stationary or atconstant velocity, or non-aligned or acting in oppositedirection of the energized accelerated self gravitatingbiomass or of the steady state supporting inertialreference frame at the specific point of time. Thus MIIseems to play anti (self) gravitational role. Without MIIsupport death occurs (Illustration 13).

We propose few more examples of metabolically inertinfrastructure, the exact role of which is so far notspecified in life science. Algae, for instance, cannotmultiply unless they get an adequate depth of liquidmedia. Bacteria cannot survive outside the culturalmedia. Virus cannot survive without the support of anyliving host. Transfer a gene from one chromosome toother is to be carr ied through plasmid orbacteriophage which is said to act as vehicle. Inbiotechnologies, an enzyme is to be coated in a porusgel or fixed to a solid support which acts as media.Similarly solid support that contains substance usuallya gel such as agar embedded in it for bacteria andyeast, nutrient broth (liquid nutrient medium) or LuriaBertani medium (LB medium or Lysogeny Broth);extracellular matrix components ; calf serum;suspension cultures; polyacrylamide gels, collagengels, and basement membrane gels at cell–substrateinterface for glioblastoma; organotypic cultures; etcare some other examples that appears to maintaininvisible separation between self gravity and mutualgravity or seclusion environment for self gravity.Intravenous drip of ‘isotonic saline’ to an ailing patientseems not only corrects disturbances in water andelectrolytic balance but also provides in limited mannerbuoyancy force to various life supporting organs orsystems against gravitational pressure. Mucilaginousjelly which surrounds the embryo in amphibians suchas frogs, toads as well as in insects possibly acts in asimilar way. Hence it can be said that role of metabolicinert infrastructure towards keeping secluded conditionfor operation of self gravity is a vital gap area ofinvestigation in biological science.

12. Behavior of living mass under different typesof medium

It is to be remembered that fluids play an importantrole towards buoyant like physical force that separateself gravitating biomass in living body from thesurrounding inertial gravitational forces, else whichmight perturb the action of self gravity. In addition tocytoplasmic and other fluid matrix in living cells,human body contains various fluids like blood plasma,lymphatic fluid, interstitial fluid, viscous fluid of mucus,saliva, gastric juice, cerebrospinal fluid, sweat, tears,the aqueous and vitreous humors of the eye, semen,



vaginal secretions, amniotic fluids etc. Thecomposition, density and depth of each fluid differaffecting operational buoyant force. For instance, brainexists in neutral buoyancy. The actual mass of thehuman brain is about 1400 grams; however, the netweight of the brain suspended in the CSF underneutral buoyancy is equivalent to a mass of 25 grams.Similarly blood cells are suspended in a fluid calledblood plasma, which is mainly composed of water anda mixture of other dissolved substances, or solutesapart from hormones, vitamins, amino acids, andantibodies. Blood plasma has a density ofapproximately 1.025 kg/l. In comparison to plasma,glucose in cerebrospinal fluid (CSF) is diminished byabout 80%. It is a gap area of investigation that howfar disturbance in operational buoyant force canperturb various activities of life processes.

Cells traditionally have been studied in two dimensions(2-D) in a petri dish, but certain cells behave differentlyin three dimensions than in two. Size and shape of the cell depend on the external biophysical forces.Cells exposed to microgravity include more rounding,loss of gravity-dependent convection, negligiblehydro-dynamic shear and lack of sedimentation34. MITbioengineers35 have provided pictures that shownormal and diseased cartilage cells which areorganized differently in normal and diseased cartilageand 3-D cell clusters of same normal and diseasedcartilage precisely re-created in a tissue like gelcompared to cells in a conventional 2-D petri dish (Illustration 14). External biophysical force is to beexamined critically for specifying behavior of the livingmass on it, especially gravitating environment towardsmaintaining seclusion.

13. Importance of medium vis-à-vis unperturbedself gravity

We have assumed that self-gravitating biomass/embryo is in the accelerated reference frame,manifesting its physiological and genetic functionality.The “Metabolically Inert Infrastructure (MII)? is placedin the co-moving non- accelerated reference framethat are relatively stationary or at constant velocity, ornon-aligned or acting in opposite direction of theenergized accelerated self gravitating biomass or ofthe steady state supporting inertial reference frame atthe specific point of time. Let us see how it appliesin case of mediums required as microbial orbiotechnological analysis protocols like agarose,polyacrylamide, silica colloidal crystal (SCC), raffinoseetc. For instance, three “blot” techniques are utilized for detecting presence and relative quantities of specific macromolecules (DNA, RNA,protein) in cells viz. DNA (Southern) with agarose/

acrylamide, RNA (Northern) with agarose, and protein(Western) with polyacrylamide. Why to be positionedover agarose or other gel? The agarose gel is across-linked matrix that is somewhat l ike athree-dimensional mesh or screen36. When boiledagarose cools, it forms a loose molecular netresembling a sponge with required mechanical rigidityin soft porous texture. The pores in the gel matrix arefilled by the liquid phase. Buoyant like force of theliquid is thus augmented by mechanical rigidity of thesurrounding structure. Thus apart from other knownadvantages, final agarose gel gets the ability towithstand compressibility and allows the positionedbiomass to feel less stressed under concentratedgravitational load (Illustrations 15).

In Southern blotting, for instance, after separation offragments according to length, a sheet of eithernitrocellulose paper or nylon paper is laid over the gel,and the separated DNA fragments are transferred tothe sheet by blotting. The gel is supported on a layerof sponge in a bath of alkali solution, and the buffer issucked through the gel and the nitrocellulose paper bypaper towels stacked on top of the nitrocellulose (Illustration 16).

As the buffer is sucked through, it denatures the DNAand transfers the single -stranded fragments from thegel to the surface of the nitrocellulose sheet, wherethey adhere firmly. Stress applied from own weightand from external load is known as effective and netstress respectively. The bulk modulus of a substance,on the other hand, measures the substance'sresistance to uniform compression or stress. Foreffective rafting, the biomass is required to besecluded, isolated or free from stress on flotation orthrough other mechanisms. Stress applied from ownweight differs among RNA, DNA and proteinfragments due to obvious reason of difference in molarmass and density. Also agarose gels have larger'pores' than polyacrylamide gels meaning that it packsless densely then an equivalent amount ofpolyacrylamide. Therefore, considering variation inpacking density, agarose is generally used for theelectrophoresis of large molecules such as DNA andRNA and polyacrylamide is used for small moleculessuch as proteins. Uneven local mass distributioncauses local variation in density as well asgravitational attraction. Accordingly choice forseclusion is being made among various availablematerials.

Evans et al37 pointed out that while cell attachmentwas unaffected by the stiffness of the growth substrate,cell spreading and cell growth were all increased as afunction of substrate stiffness and the mechanical



environment can play a role in both early and terminalembryonic stem cells (ESC) differentiation. Ji L et all38

found that cells cultured on the substrates formedof silica colloidal crystal (SCC) retained transcription ofstem cell and endoderm markers more similar toundifferentiated ESCs, suggesting the substrates arerestricting differentiation, particularly towards theendoderm lineage, compared to cells cultured on flatglass. Additionally, five days after seeding, theyobserved strikingly different colony morphology, withcells on the SCC substrates growing in sphericalcolonies approximately ten cells thick, while cells onglass were growing in flat monolayers. Colonies on theSCC substrates developed a central pit, which wasnever observed in cells cultured on glass, andexpressed proteins related to epithelialisation.Together, these data demonstrate the potential ofusing topographical cues to control stem cellbehaviour in vitro. For smallest prion39, say ([Het-s]prion (molecular weight of 35-36kDa) of thefilamentous fungus Podospora anserina transformantsare grown in liquid raffinose synthetic medium (SR)plus galactose. As stated above, molar mass ofraffinose, a trisaccharide composed of galactose,fructose, and glucose is 504.42 g/mol with density1.723 g/cm3. Therefore it seems that medium plays avital role towards unperturbed action of self gravity.For smallest prion, a protein, liquid reffinose, acarbohydrate is sufficient to increase density of theliquid medium and thereby provide a separation due topressure of up thrust from inertial gravity, where as forDNA, RNA, larger proteins, whose molecular weightand density is comparatively higher, mechanical propup support from agarose gels etc. is additionallyrequired. However all these are gap areas ofinvestigation.

Metabolic Energy and SelfGravity

14. Whether gravitational anchor is a criterion formanifestation as living?

It is theorized that a single cell is difficult to surviveunder na tu ra l cond i t i on w i thou t be ingself-gravitationally anchored or attaining steady statecondition or under multi-assembled single cellcondition. A single cell cannot survive in isolated way,unless it is anchored by inertia. A minimal inertialmass is required for survival. In plant tissue culture,unless a callus (“explants”) of say above 500 mg40 orsuspension of cultures of say, 3-4 cubic centimeter (interms of PCV - packed cell volume) is used, it is

difficult to maintain continuity of life and growth fromindividual cells. Similarly in the final volume for cellculture, maintaining cell density as low as 3 x 105 tohigh of more than 10–15x 106 cells/ml of inoculumsare required. Why a minimum mass is required for cellculture under multi-assembled single cell condition. Isit for anchorage? There is a literary proverb that “ARolling stone gathers no moss”. This is not only aliterary proverb but based on scientific observation andfact of the commoners.

As biomass possesses both gravity and inertia, it hasthe characteristic that it can act as anchor as if entirebiomass is concentrated at the centre or at theequilibrium point. Thus after seclusion, unless abiomass is anchored or pivoted in a steady statecondition through the action of inertia, attainment ofaccelerated condition would be difficult. This is similarto frictional force (force resisting the relative motion oftwo surfaces in contact) between feet and ground insteady state condition required for smooth walking.Mitochondria, a primary energy producer in the cell,constantly change shape, i.e. it remains in motion.Electron transport chain would be away from centralcore of a self gravitating cell, as the intensity ofgravitational energy gets reduced from the core to theperiphery when it can be overpowered by electrostaticforce (Illustration 17). Therefore we can propose thatcritical quantity of biomass is important for acting asinertia upon which mechanism of self gravity canoperate i.e. further growth is possible on anchorage.

15. Energy producing organelles or sites locatedaway from the centre

Normally carbohydrate is considered as main sourceof energy for biological mass. One gram ofcarbohydrate on oxidation in the body duringrespiration gives about 17000 joules of energy,whereas 1 gram of fat gives about 37000 joules ofenergy. ATP is produced through four basic methods:in bacterial cell walls, in the cytoplasm byphotosynthesis, in chloroplasts, and in mitochondria.However, energy producing organelles or sites islocated generally away from the centre of self gravityof a cell or away from the central axis of the biomassin a reference frame at that point of time (Illustration18).

16. Some anomalous hypothecations in healthscience

We have noticed some anomalous hypothecation inhealth science on describing mass or weight viz. indescribing Body Mass Index (BMI), Body Surface Area(BSA). Basal Metabolic Rate (BMR), RestingMetabolic Rate (RMR); Physical Activity Level (PAL),



Lean Body Mass (LBM) are the most popularanswered phenomena in life science. These areexplained in details below with the invitation forformulating correct hypothecation in the light of selfgravitation bio.

17. Body Mass Index (BMI)

Body Mass Index (BMI) or Quetelet index 41, remains acontroversial statistical measurement of health. Bodymass index is defined as the individual's body weightdivided by the square of his or her height. {BMI=Weight (kg)/ height2 (m2)}. The WHO regards a BMI ofless than 18.5 as underweight and may indicatemalnutrition, or other health problems, while a BMIgreater than 25 is considered overweight and above30 is considered obese42. BMI determine risk ofdeveloping heart disease and other health problemssuch as diabetes. BMI

As per ‘Self Gravitation Bio’, BMI is nothing but weight/height or mass/volume = density of the body mass. Itgives indication for quantum of self gravitationalattraction, as density of the mass is importantdeterminant for gravitational potential energy. Age, aninfluencing factor of BMI, could be taken as thecapacity to generate metabolic kinetic energy. Otherinfluential factors include gender and accumulation offat (adipose tissue) in individual body is primarily areflection of differences in body mass and density.Once presence of self gravity is resolved in individualbody, other factors can automatically be laid to rest onmeticulous study in right perspective.

18. Body Surface Area (BSA)

Weight can be a measure for gravitational force over amass. It cannot be a measure for ‘surface area’. Butin calculating Body Surface Area (BSA), healthspecialist has to take into account of the totalgravitation force with incorrect nomenclature as‘surface area’ as reflected in equations from (4) to (9)below. Let us see how and why it happens. BodySurface Area (BSA) is used to measure renal function-glomerular filtration rate (GFR), to calculate cardiacindex (cardiac output/BSA), Chemotherapy &Glucocorticoid dosing. Body surface area (BSA) isconsidered "normal”- 1.7 m², average (men) 1.9 m²,(women) 1.6 m²; child (9 years): 1.07 m², (10 years)1.14 m²; (12-13 years): 1.33 m²; neonate: 0.25; 2 year:0.5 m2.

But BSA remains controversial starting in 1916 withthe Dubois & Dubois formula 43, (Illustration 49 Equation 5)

A commonly used formula is the Mosteller formula 44,published in 1987: (area in sq m from weight in kg andheight in cm): (Illustration 49 Equation 6)

Haycock formula (in children) 45: (Illustration 49 Equation 7)

Gehan & George formula46 (Illustration 49 Equation 8)

Boyd's formula47: (Illustration 49 Equation 9)

National Cancer Institute (Illustration 49 Equation 10)

From the above, it is clear that there should be acorrection in our concept on body surface area withself gravitation bio.

19. Basal Metabolic Rate (BMR)

Basal metabolic rate (BMR) remains controversial forlong with no satisfactory solution at sight withinexisting principles. BMR is considered as the amountof energy expended while at rest in a neutrallytemperate environment, in the post-absorptive state(meaning that the digestive system is inactive, whichrequires about twelve hours of fasting in humans). Therelease of energy in this state is sufficient only for thefunctioning of the vital organs, such as the heart, lungs,brain and the rest of the nervous system, liver, kidneys,sex organs, muscles and skin. BMR decreases withage and with the loss of lean body mass. Increasedmuscle mass can increase BMR. Aerobic fitness level,a product of cardiovascular exercise, while previouslythought to have effect on basal or resting metabolicrate (RMR), has been shown in the 1990s not tocorrelate with BMR. BMR is measured under veryrestrictive circumstances when a person is awake, butat complete rest. An accurate BMR measurementrequires that the person's sympathetic nervous systemnot to be stimulated.

In fact, in absence of proper viewing perspective overthe definition of ‘mass’, as measure of gravitationalforce, calculation of metabolic rate remainscontroversial from 1880 till date. Max Rubner (1880)48

reported that mammalian BMR is proportional to Mass 2/3.Kleiber (1932)49 supported by Brody (1945)50 modifiedproportionality to Mass ¾. Several other predictionequations also came into being. Historically mostnotable was Harris-Benedict equation51, which wascreated in 1919:

for men, (Illustration 49 Equation 11a)

for women, (Illustration 49 Equation 11b)

where P is total heat production at complete rest, m isthe weight, h is the stature (height), and a is the age,and with the difference in BMR for men and womenbeing mainly due to differences in body weight. In fact,we are of the opinion that mechano-structuraldifference between genital organs of men and womenprimarily lies mostly with the extrovert and introvertexpression respectively of the soft matter during theformative stage, on which we are constrained to



elaborate at present except requesting for detailedmechanical analysis on four dimensional structuralfeatures of men and women. However for purpose ofestimation of BMR, Harris-Benedict equationwas thebest prediction equation until recently, when MD Mifflinand ST St Jeor in 199052 created new equation: (Illustration 49 Equation 12)

where s is +5 for males and −161 for female.

BMR was also attempted to be correlated with changein life style. It was stated that during the last 100 years,lifestyles have changed. A survey in 2005 53 showedthat it is about 5% more accurate. These formulae arebased on body weight, which does not take intoaccount the difference in metabolic activity betweenlean body mass and body fat. A more accurateformula is the Katch-McArdle formula54 based on leanbody mass: (Illustration 49 Equation 13)

where LBM is the lean body mass in kg.

In the mean time other issues goes on hunting lifescience researchers. In both endothermic andectothermic animals, the normal metabolic rate isinversely related to body size; the smaller theorganism, the higher the relative metabolic rate. Whiledealing endothermic and ectothermic animals,naturally temperature has been brought into thescenario. But here also what is true for endotherms isnot applicable for ectotherms. For instance,temperature is considered as an important factor inenzyme activity. It is speculated that as thetemperature increases up to about 40oC, the velocityof an enzyme-catalyzed reaction increases becausethe substrates collide with active sites more frequentlyas the molecules move more rapidly due to thermalagitation55. Because the metabolic reactions areenzyme catalyzed, metabolic rate would beproportional to temperature, up to the point where theenzyme is denatured. The relationship betweenmetabolic rate and temperature is often expressed asQ10, which measures the rate increase for each 10o

rise in temperature. It is contemplated that the abruptdecline above 40o represents the point at which theweak bonds that hold enzymes in their specific activeconformations begin to break. As a result the enzymesbecome denatured and metabolic activity is severelydisrupted. Enzyme is a class of protein. We havedealt protein denaturation with rise in temperature andits relation with self gravity subsequently.

Inverse relationship between metabolic rate and bodysize was said to be easily understood in the case ofendotherms; stating that smaller animals have agreater surface-to-volume ratio, and consequently alarger relative heat loss to the environment per unit

time55. To maintain a constant high body temperaturedespite rapid heat loss across a body surface, a smallanimal ought to oxidize food at a high rate. Becausethe relative amount of food consumed and the pace ofdigestion, respiration, and so on must rise withdecreasing body size, there is a lower limit on the sizeof endotherms. The smallest mammals weighing onlyabout 4 grams are required to eat nearly their ownbody weight of food every day, and can starve todeath in just a few hours if deprived of food.

In case of ectothermic animals, the same principledoes not hold. Ectotherms lose their metabolic heat tothe environment and do not normally respond to heatloss by increased metabolism, so larger size and itsconcomitant smaller surface-to-volume ratio shouldactually retard heat loss somewhat, and the conservedheat ought then to speed up metabolism. It is thoughtthat increasing size involves a disproportionateincrease in the mass of skeletal and other connectivetissue in animals—an alligator, for instance, requiresmore inactive support structure than a salamander.Since these t issues are relatively inactivemetabolically, the average metabolic rate per unitweight for the organism as a whole may fall as theproportion of these less active but necessary structuraltissues rises55.

Larger animals have relatively slower metabolismsthan small ones. A mouse must eat about a third of itsbody mass every day not to starve whereas a humancan survive only on 2%. The relationship follows apower law: basal metabolic rate (R) is proportional tothe ¾ power of an animal's mass (M). This relationship,the Kleiber Law49, 50, can be drawn as a straight line ona log-log plot (Illustration 19). Mysteriously, this simplerelationship holds, from simple organisms to mostcomplex ones, from microbes to giant blue whalesacross 18 orders of magnitude in body mass55.

To arrive at conclusion, some ambitious researchers56

proposed a concept based on analysis of circulatorysystem to explain how characteristics like body sizeand energy consumption differ from species to speciesalong fixed scales. Their scaling was based on somesmall to huge animal to demonstrate mathematicaland geometric nature of networks that distributenutrients and carry away waste and heat. The biggerthe animal, more efficient it uses energy (Illustration 20). Unfortunately such mathematical and geometricalscaling concept also seems did not work in greatercontext of family for living organisms.

Barbara Fischer of the theoretical population ecologyand evolution group, Biology Dept., Lund University57

however stressed on a unifying principle of ecologywith the ‘metabolic theory of ecology’. It states that



metabolism provides the fundamental constraints bywhich ecological processes are governed. It suggeststhat from single organism’s life-history strategies topopulation dynamics and ecosystem processes at alllevels of organization could possibly be explained interms of constraints imposed by metabolic rate.

Now question arises, who could impose so called‘constraints’ over metabolic rate? Universally gravity isthe known ‘culprit’ (?) which often put constraints inour activities. As stated above, mass and metabolicrate is inversely related. That is, ‘mass’ or in otherterm ‘gravity’ itself might not allow metabolic energy toact in unlimited manner. In one hand, part of mass(say 2/3 to ¾ or 66 to75%) is expended towardsmaintaining metabolic rate. On other hand, we knowthat 100 percent of the same mass works towardsgenerating self gravitational potential energy. There isthus a huge difference between kinetic (metabolic) andpotential (gravitational) energies. We are fortunate tosay that inertia of gravitational potential energy plays aleveling ground for balancing gravity’s compressiverole on putting limitation. The metabolic energy is thuson a tug-of-war between potential and its own kineticenergy. When force of gravity and inertia arebalanced there will be no change of motion. With suchbalanced force, motion of the object remainsstationary i.e. net force is zero. When metabolicenergy is put at the rate of 10-12 to 10-6 kcal/hr, it canmove unicellular organisms. It would have to workagainst both intrinsic and extrinsic gravity (if notremains in secluded condition). Similarly cold bloodedanimals can be in motion against self gravity andplanetary gravity, when metabolic rate is 10-8 to about100 kcal/hr. Warm blooded animals do the same workwith metabolic rate having less than 100 to 103 kcal/hr.Under secluded condition, some exception may occurwhen due to upward force of fluid, the animal wouldrequire less energy compared to energy requirementof same mass in land. Thus presence of metabolicenergy can be felt taking into account both intrinsicand extrinsic ‘gravitational force’ with resting metabolicrate (RMR) for meeting most of the demands onworking against self gravity where as physical activitylevel (PAL) could be mostly to meet demands forworking against extrinsic gravitational force. This willbe clear from the under mentioned discussions.

Take an example on movement of human thoracicdiaphragm. We will discuss subsequently the origin ofits dome shape arc structure, the issue of maintainingconstant angle between radius from the commoncentre and tangents (over intercepted arc). Herepotential energy of self gravity contracts its domeshape structure. The inertia attempts to bring back

contracting surface to original position. Kinetic energyof metabolism works against it, thereby, allowing thedome shape structure to relax. Unbalanced forcescauses change in motion in a curved surface inspeeding up and slowing down (Illustration 21).Resting metabolic rate (RMR) is therefore primarilyinvolved in such internal activity against self gravity.

On the other hand, raising a ball through a heightabove earth’s surface by hand involves metabolickinetic energy against potential energy of earth’sgravity and invites spending metabolic energy as perphysical activity level (PAL) on contracting andrelaxing muscles (Illustration 22).

Thus understanding distribution of metabolic energy towork against self gravity and planetary gravity, role ofpotential and kinetic energy including inertia is a majorgap area of investigation in life science. It would notonly clear all ambiguity towards basal metabolic rate(BMR) but also serve as a precursor of various newresearches in biological science including health ofhuman, animal, plant and microbes.

Centre of self Gravity

20. Why central position is vital?

The central position in a gravitating system would beas if the entire mass in the sphere of influence wouldhave been concentrated at that point, a distinguishablefeatures of gravitational force from other basic forcesviz. electromagnetic forces or any other local forceslike surface tension, elastic forces etc. (Illustration 23).

21. Why nucleoid, nucleolis or nucleus tend toremain in central position?

Why nucleoid in prokaryote and nucleolis or nucleus ineukaryote, all which are made of swarm ofmacromolecules and little denser in the spatialdistribution than the surrounding cytoplasmic matrix,attempt to remain in central position of the cell? (Illustration 24)

22. Generation of ‘muscle tone’ remains elusive inhuman physiology

Muscle tone or background tensions remain elusive inhuman physiology. In the book “Fundamentals ofNeurophysiology” Robert F. Schmidt pointed out that“Summation of the twitches of many fibers, excitedasynchronously at low frequencies up to 5/second,generates a total force that does not fluctuate verymuch, with amplitude that must be approximatelyproportional to the average frequency of excitation.The ‘background’ tension produced in this way by



summation of the twitches of many fibers is called tone.All the muscles in a living organism possess such tone.Even in a relaxed limb, the motor nerves are activatedat low frequency.” Gray’s Anatomy empirically deniesexistence of muscle tone, as it doesn’t show up on anelectromyography. But Gray’s anatomy admitted thatan electromyograph can’t pick up low level,steady-state action unless the motor units immediatelyadjacent to the contact are firing. It just reads asbackground noise. Other authors postulate that thereis an inherent elasticity in the muscles, and still otherstalk about muscle tone but don’t have a clear picture ofwhat it is. Interestingly no one denies existence ofstatic and balanced. It is stated that tone works 24hours a day. What force would make it functionalcontinuously? The nerve impulse is primarily anelectrical event. Each neuron is like a tiny biologicalbattery ready to be discharged. It requires to becharged constantly. As life process starts withaccumulation of mass, upon which force of gravitynaturally works for 24 hours without any externalinputs. Can it be responsible for subtle tone in a body?Let us examine the issue in little details.

23. ‘Build-up’ & ‘break-down’ mechanisms inliving mass

There are two inverse-square central forces such asthe gravitational or electrostatic potential. Gravitationalfields have the same range as electromagnetic fields.The gravitational field is much weaker than theelectromagnetic field. The positive and negativecharges of the electromagnetic field tend tocompensate each other's fields. But masses are notcompensated for which gravitational force cannot becompensated. However notice to gravitational forcegets evaded. But when there could be a difference inthe quantity of mass within a span of t ime,manifestation in the variation of gravitational bindingenergy58 according to gravitational mass would bespectacular. Let us note that non-living objects havegot no ‘build-up’ and ‘break-down’ mechanisms ofcarbohydrates in mass. It is static mass. In livingobjects, on the other hand, there is change of massthrough ‘build-up’ and ‘break-down’ mechanism ofcarbohydrates59. It is a unique character that operatesin regular manner in all living objects. Photosynthesisand respiration are two alternate processes in plantswherein photosynthesis means gain (‘build-up’) inbiomass whereas carbohydrates expended duringrespiration and growth is loss (‘break-down’) of massper unit area. Adenosine 5′-triphosphate (ATP) plays acentral role in ‘build-up’ and ‘break-down’ mechanismprocess of mass in all living organisms. Thus it can beseen that in non-living matter, mass remains constant

whereas in living matters quantity of mass in the formbody weight and composition (density) gets changedwith the changes in the state of energy in the form ofbiochemical products and with the gain or release oftemperature.

24. Spectacular action of self gravity in muscletone while living and not when dead

Now let us see what would happen if there is loss andgain in living mass along with time in a self gravitatingenvironment. The change in mass in a membranebound self gravitating close structured living objectswould cause change in gravitational binding energyresulting into a source of potential energy as well asinertia. Metabolic energy primarily acts as source ofkinetic energy. This would create a tension within themass say, in the muscles fibers, vessels etc. makingthese lengthened followed by shortened, or tightfollowed by loose, or stretched followed by slack, orfirm followed by flaccid, rigid or tautness followed byflexible and so on, as per location and structuralanatomy of the particular vessel or muscle. Thisalternate movement might manifest as beats, orexcited asynchronously at low frequencies in additionto increase or decrease in potential gravitationalcompression and kinetic relaxation energy due toinertia plus metabolic energy. Such variation in theinternal pressure due to variation in potential andkinetic energy might be the source of power for givingnon-neural background tension or tone to the body.However this would be an interesting area of researchfor biophysicists.

25. There is no complete loss of tone duringparalysis

Let us cite few examples below to show howgeneration of muscle tone or background tensionremains an elusive till date. Paralysis is the loss orimpairment of motor function in a part due to a lesionof the neural or muscular mechanism. Paralysis ismost often caused by damage in the nervous system,especial ly the spinal cord. I t takes aboutone-thousandth of a second for a neuron to fire animpulse and return to its resting level. Bothsympathetic and parasympathetic neurons have aconstant rate of firing under normal conditions. This isalso called their "tone", but of neural origin. Itmaintains the normal rate of heartbeat, keeps bloodpressure within a normal range and maintainhomeostasis. Of course, the sympathetic andparasympathetic firing rate changes greatly duringfight-or-flight responses. Paralyzed muscle may beflaccid, flabby, and without appreciable tone, or it maybe spastic, tight, and with abnormally high tone thatincreases when the muscle is moved. But most



interesting fact is that there is no complete loss ofbackground tone during paralysis. Complete loss oftone is only available with death.

26. Tone is lost after death during pallor mortisand not while living

As per Law of Laplac60, (Illustration 49 Equation 14)

where T= ‘wall tension’, p = pressure, r = radius, t =wall thickness. For a given pressure, increased radiusrequires increased wall thickness to accommodate astable ‘wall tension’; also, increased pressure requiresincreased thickness to maintain a stable ‘wall tension’.The Law of Laplace explains various phenomenaencountered in the pathology of vascular orgastrointestinal walls. The ‘wall tension’ is said torepresent the muscular tension on the wall of thevessel. But how far it is true? Who controls the ‘walltension’ is not yet meticulously studied taking intoaccount the presence of self gravity. Break down of‘wall tension’ is conspicuous only after death. We willdiscuss the issue in subsequent paragraphs.

Generally the tone is said to be ‘regulated’ (decreasedor increased) by virtue of sympathetic andparasympathetic supply. The autonomic nervoussystem (ANS) operates without conscious control,relying upon reflex arcs that are dependent uponhypothalamus and medulla for overriding control.Autonomic nerve fibers innervate cardiac muscle,smooth muscle, and glands. Through these fibers theANS said to play a role in regulating blood pressureand flow, gastrointestinal movements and secretions,body temperature, bronchial dilation, blood glucoselevels, metabolism, micturition and defecation, pupillary light and accommodation reflexes, andglandular secretions, just to name a few. A mechanicalengineer will however view in different angle tounearth the word ‘regulation’.

For instance, geared elevator system (lift) works on anumber of engineering principles. Electric motor turnsthe gear that rotates the sheave. A sheave is just apulley with grooves around the circumference. Sheave grips the hoist ropes which are connected tocounterweight (Illustration 25 left). It is thereforetechnically wrong to say, elevator is regulated byelectrical force. It only regulates gear. Similarly it isincorrect to say that nervous system regulates varioushuman physical activities. Electrostatic nervoussystem cannot have ‘load’ or ‘weight’ bearing capacity.It can at best act as trigger to propel a part of themechanical system for lifting of load. It is thereforeadvisable to understand the mechanical system as awhole to ascertain ‘cause-effect’ relations in lifescience in better manner. Correspondingly a rescuer

can easily drag a drowning person in water by holdinghis hair or bathing suit. But same thing is not possiblein terrestrial environment (Illustration 25 right). Reasonis obvious.

Now let us return back to our original contention. Within minutes of the heart stopping, a process calledpallor mortis61, blood drains from the smaller veins inthe skin. That is its original background tone is lost.Therefore question arises why tone is lost afterheart-beating death62, 63 during pallor mortis and notwhile living? Why nerve impulse fails to act whenclinically dead. Loss of tone is related to potential andkinetic energy of mass. This small difference in thepathology of paralysis and death needs thoroughinvestigation.

27. Intrinsic muscle tone is constantly maintainedwhen living but loose after death

We see that intrinsic muscle tone is maintained for 24hours when living. After death, intrinsic muscle tone islost. For example, due to the tone in the longitudinalmuscle bundles in the gut, the length of the smallintestine remains at half while living. After death gutlength becomes double, say about 24 ft. Duringparalysis such an event is rare. At the moment ofdeath, all of the muscles in the body relax, a statecalled primary flaccidity. Eyelids lose their tension, thepupils dilate, the jaw might fall open, and the body'sjoints and limbs are flexible. With the loss of tension inthe muscles, the skin will sag, which can causeprominent joints and bones in the body, such as thejaw or hips, to become pronounced.

28. Edema occurs in lowers or dependant parts ofthe body after death

After 2 to 6 hours of death, external gravity begins topull blood to the areas of the body closest to theground, a process called livor mortis. Hypostasis orsettling of blood and the dependent edema i.e. fluids inlower or dependent parts of an organ or body occursafter death. Why downward pull towards externaldirection? Why such severe manifestation of earth’sgravity is not pronounced while living? In fact whileliving, full tone could be maintained when there is abalance between potential energy of self gravity andkinetic energy of metabolism within self gravitatingenvironment. But with loss of such equilibrium,extrinsic (earth’s) gravity could pull down fluids, bloodin the direction of stronger external gravity, asdescribed above and the organism behaves as inerton losing its tone (Illustration 26).

29. Intuitive model on generation of ‘backgroundtone’

Muscle tone64 is usually defined as the amount of



contraction in a resting muscle. It is a static, balanced,isometric contraction between agonist and antagonist(both internal forces) in every muscle in the body. Itnever lets go completely, even in sleep, when alldynamic muscle activity is gone. It operates when onedoes nothing. Muscle-building exercise elevates tone,can even slam it up considerably, but at whatever levelthe involvement of contraction, tone still remains staticand constant at any given time.

It is argued that between cardiac and flat muscles, flatmuscles resist becoming hypertonic. They can’tsqueeze off their veins so they can’t encapsulate lacticacid. Cardiac muscle is non-spastic because it canburn lactic acid. However exhalation and inhalationmechanism is based on thin dome-shaped sheet ofmuscle of the thoracic diaphragm which is said to becontrolled by phrenic nerve. It is to be rememberedthat electrostatic nervous system can regulatephysiological process but when the question ofbearing certain ‘load’, its controlling role would belimited. Therefore unless a mechanism similar topneumatic system operates, simple nerve impulsecannot control movement of load. This is a grossoversight in life science.

Thoracic diaphragm is kidney shaped in outline andhas the ability to contract from its edges towards itscentre. Its centre lies horizontally across the bodydividing the trunk into two compartments: the thorax(the chest) and the abdomen (the belly). The thoraxcontains the heart and lungs while the abdomencontains the organs of digestion. Geometrically domeshaped structure is an intercepted arc, centre point ofwhich is coinciding somewhere in the imaginary centreof self gravity as per human architecture. Potentialenergy (compressive) of self gravity contracts thedome shape structure. Kinetic energy decompresses,thereby allowing the dome shape structure to relax.While undertaking both contracting and relaxedcondition, it is maintaining a constant angle betweenradius from the common centre and tangents (fromintercepted arc), as shown in left side of the illustration(Illustration 27). Similarly, if tangents are drawn on thecircumference (intercepted arc) of the balloon likeinflated heart, these will also form constant angles withthe radius from the centre of the structure duringembryonic stage65. The alternate ‘half-bulging’structure in the muscles is available around skeleton inthe periphery on one side of a joint and end via atendon or ligament on another side of the joint,functioned by sympathetic and parasympatheticnerves. If tangents are drawn over such alternate‘half-bulging’ intercepted arc, there also constantangles can be seen between tangent and radius

drawn from central position, as shown in the middle ofthe illustration (Illustration 27). Thus it is apparent thatthe basic geometrical structure of different organs/mechanisms in human coincides with the centre andrelated features of potential energy of self gravity (U =mgh) and kinetic energy (Ek = ½ mv2) against it.Manifestation of background low frequency ‘muscletone’ is the interaction between self gravitationalbinding (potential) energy and metabolic (kinetic)energy against potential energy. Hence selfgravitational potential energy balance66, 67 needs to beworked out in human axisymmetric con?gurationstructured under stratified density of soft matter orfluids where viscous forces may play to createdivergent geometry at early stage of formation.

Under equilibrium condition between potential andkinetic energy, muscle tone would remain static andbalanced from centre to periphery. Undernon-equilibrium condition, especially due todisproportionate build-up of mass, self gravitationaltone or background tension would increase fromperiphery to the centre, leading to various collapse inliving mechanism. The close relation between obesityand cardiometabolic syndrome 68, 69 may be cited as anexample. Thus we find that “balance is the law of life”,though we are to move with unbalanced potentialenergy with the kinetic energy.

30. Abundance of logarithmic spiral in naturevis-à-vis self gravitating phenomena

It is interesting to note that gravitational waves workslike water, sound and electromagnetic waves and isable to carry energy, momentum, and angularmomentum from their sources. Very low frequencywaves may be impossible to detect but it seems thatthere is some indirect evidence for its existence. Forinstance logarithmic spiral70 is also known as thegrowth spiral, equiangular spiral or spira mirabilis. Thelength of the radius goes on increasing with the shell. The logarithmic spiral has the unique property ofmaintaining a constant angle between the radius andthe tangent at any point on the curve (Illustration 28).This spiral is related to Fibonacci numbers, goldenratio, or golden spiral in snails, snakes and others.Unless mechanism of potential energy of self gravityversus kinetic energy of metabolism is not brought intothe scenario, formation of logarithmic spirals in naturewill continue to remain elusive.

31. Human average body frequency

Various persons viz. Bruce Tainio, Dr. Royal R. Rife,Nikola Tesla, Dr. Robert O. Becker had stated to havebuilt frequency generator, frequency monitor andclaimed71 to have found that in a healthy body average



frequency is 62-72 Hz . When the frequency drops, theimmune system is said to be compromised. We do notlike to comment in favor or against such claim. Ratherwe suggest that under strict scientific procedure athorough investigation could be made. Earlier peoplewere conversant with the frequencies of the electricaland magnetic forces. So their analyses were reflectedin their thinking. Now when there is a possibility ofgenerating frequency due to inward breakdown andoutward buildup mechanisms with the force of selfgravity, the matter may be reinvestigated. It is toremember that angular velocity, angular frequency andhertz all have the dimensions of 1/s, angular velocityand angular frequency are not expressed in hertz, butrather in an appropriate angular unit such asradians per second. Thus a disc rotating at 60revolutions per minute (rpm) is said to be rotating ateither 2π rad/s or 1 Hz, where the former measuresthe angular velocity and the latter reflects the numberof complete revolutions per second. The conversionbetween a frequency f measured in hertz and anangular velocity ω measured in radians per second are(Illustration 49 Equation 15):

S i m i l a r l y h i g h e r f r e q u e n c i e s o f t h equantum-mechanical wave functions of high-energyare expressed in terms of equivalent quantum energy,which is proportional to the frequency by the factor ofPlanck's constant. Can we therefore think that low andhigh frequency could possibly be a differential featurebetween self gravitational waves and electrical waves?(Illustration 29) Thus there is ample opportunity todetect the frequency of gravitational waves atmesoscopic length scale on the principle ofequivalence in tune with macroscopic and microscopicscales.

32. Body cools down on death after loss ofcontraction-relaxation of self gravity

After death, the human body begins to cool down fromits normal temperature of 37° Celsius until reachingthe ambient temperature around it. Known as algormortis, the decrease in body temperature follows asomewhat linear progression. Decrease in bodytemperature is two degrees Celsius in the first hour;one degree each hour thereafter. Let us see how thissituation can happen? In a self gravitating environment,on collusion between random molecules duecontraction and relaxation mechanism throughalternate ‘build-up’ and ‘break-down’ processes ofmass, body temperature gets elevated. But when selfgravity loses such contraction and relaxation process,the speed of corresponding molecules gets slowerwith loss of mobility and resistance, resulting in fall inbody temperature with death. Thus loss of mechanism

of self gravity means motion of molecules gets restand random motion of molecules that endows with theproperty of temperature gets die down. Duringneural-regulated paralysis, temporary or permanent,there is no such spectacular fall in body temperature.The fall in body temperature is spectacular only afterself gravity loses its strength and gets mingled withexternal gravity of the earth. Unless the mechanism ofself gravity is not brought into the life science scenario,rise and fall in body temperature of living organismswill remain elusive.

33. Which force regulates stretching andrelaxation during esophageal peristalsis?

An interesting study on the effect of earth’s gravity onesophageal peristalsis in humans was studied72. Manymammalian species including non-human primatesconsume water in a body position not aided by earth’sgravity and it has been conjectured that esophagealperistalsis overcomes earth’s gravity in humans. Letus then examine the peristaltic phenomena in the lightof self gravity. The esophageal wall is composed ofdistinct layers- outer longitudinal muscles and innercircular muscles. The function of outer longitudinallyoriented muscle layer is yet unclear72, but it is stated tobe involved in inner mucosal movement. Sequentialcontraction of longitudinal muscle occurs duringperistalsis. This is stated to serve in order to shortenthe esophagus and increase the cross-sectionaldiameter, thereby facilitating bolus transport. William G.Paterson73 while reviewing the whole process pointedout that much remains to be learned about thephysiologic control of esophageal peristalsis. At rest itmay contract in a cyclical pattern. Intracellularr e c o r d i n g s h a v e r e v e a l e d r h y t h m i cdepolarization-repolarization with a frequency of 2 to3/min. The duration of contraction also appears to varyalong the esophagus. Contraction is longer distally(away from the center of the body) than proximally(nearer to the center of the body). The peristalticvelocity averages about 3 cm/sec in the upperesophagus, then accelerates to about 5 cm/sec in themid-esophagus, and slows again to approximately 2.5cm/sec distally. Why such positional variation e.g.rapid in proximally and slower in distal? Unless selfgravity which is stronger at centre and weaker atperiphery or at distal points is not brought into thescenario, it will remain elusive in spite of presence ofmyenteric plexus over the whole gut.

The primary origin of push-pull travel force withalternate stretching and compression from theperipheral to central direction can be apparently seenin foetus position (Illustration 30). Compression andresultant stretched force due to inertia and action of



the self gravity is apparently available from mouth tostomach, considering a point somewhere aroundstomach as the central position and mouth as well asanus as in the periphery of the self gravitating body.Centre being higher compressive zone, peristalticvelocity will be higher proximally than the periphery.Thus origin of the peristaltic movement for longitudinalmuscle with push-pull travel force can become clearwith the introduction of self gravity. However this is agap area of investigation.

34. What causes channel narrowed or dilatedduring trafficking?

There are many instances of constriction and dilationin channel movements in trafficking in both animalsand plants. But in most of the cases these are in halfway to give a complete understanding. In the plant cellwall, for instance, plasmodesmata are channels that inconjunction with associated phloem form anintercellular communication network that supports thecell-to-cell and long-distance trafficking of a widespec t rum o f endogenous p ro te ins andribonucleoprotein complexes. The narrowed anddilated route of trafficking of such macromolecules isof importance in the orchestration of non-cellautonomous developmental and physiologicalprocesses. Plant viruses encode movement proteinsthat subvert this communication network to facilitatethe spread of infection74. Macromolecules moveaccording to electrochemical gradient andhydrodynamic (Stokes) radius. Plasmodesmata andmore specifically constriction and openness ofdesmotubule in mesophyll cells of plants is regardedyet an unknown function.(Illustration 31) Whichspace-time bound pressure control hydrodynamicradius at various strategic locations? This is a gaparea of investigation in the light of self gravitatingenvironment.

35. Why nuclear-cytoplasmic ratio is important forhealth?

Hypotonic, isotonic and hypertonic solutions are usedfor making cell turgid, flaccid and plasmolyzedrespectively on adjusting its volume. Thereforevolume regulation is important and vital in cellularresponse under aqueous media. Tonicity of aqueoussolutions (water with solutes, such as salt, dissolved init) is based on cellular responses to that solution.Solutions are hypotonic if the cells or tissue swell inresponse to immersion. Solutions are isotonic if thecells or tissue neither shrinks nor swells in response toimmersion in that solution. Solutions are hypertonic ifthe cells or tissue shrink in response to immersion. Why volume regulations in the overall passage routeand in the overall size of the inner macromolecule are

important? Why any physical imbalances between thetwo as regards their sizes create health hazards?Control of sizes of inner macromolecules may behydrodynamic based on tonicity (Illustration 32), butwhat about overall size of the trafficking route? Whichfactor control size of the trafficking route? This is a gaparea of investigation.

The nuclear-cytoplasmic ratio is a ratio of the size (i.e.,volume) of the nucleus of a cell to the size of thecytoplasm of that cell. The nuclear-cytoplasmic ratioindicates maturity of a cell, because as a cell maturesthe size of its nucleus generally decreases. Why sizeof the nucleus should decrease with maturity? Thephenomena can better be answered with the conceptof self gravity. Self gravitational pressure actinginwards thought to be exerted on the surface outside. Thus it could squeeze fluids and gas out of the surface.Such squeezing action would be maximum at thenucleus, as if a core segment in a self gravitating body.Maturity means an increase in mass with increase indensity. More the mass with increase in density morewould be the squeezing action, as per classicalgravitational law. Ratio is fairly constant for a particularcell type.

An increased nuclear-cytoplasmic ratio is commonlyassociated with precancerous dysplasia as well aswith malignant cells. For example, "blast" forms oferythrocytes, leukocytes, and mega karyocytes startwith an N:C ratio of 4:1, which decreases as theymature to 2:1 or even 1:1 (with exceptions for maturethrombocytes and erythrocytes, which are anuclearcells, and mature lymphocytes, which only decrease toa 3:1 ratio and often retain the original 4:1 ratio)75. Oncorrecting cytoplsmic density with addition ofhypertonic, isotonic or isotonic normal saline thusregulate nuclear cytoplasmic ratio. For instance, tumorcell morphology was visualised76 through use oftransmission electron microscopy following 1 hourexposure to a hypertonic environment. The cells in ahypertonic environment exhibited a reduction innuclear/cytoplasmic ratio, well defined plasmamembranes and contained intact organelles with noevidence of nuclear condensation or apoptotic bodies (Illustration 33). This is indicative that buoyed up forceof the fluid can be manipulated within the stipulatedvolume of the cell to get desired size of the nucleus,through process of osmosis and diffusion.

36. Matching inward wall pressure in cellularactivity vis-à-vis self gravity

Turgor Pressure is the support for plants generated bywall pressures. Water enters the cell by osmosis fromthe higher osmotic potential (solute potential) to thelower osmotic potential. The volume of the cell



cytoplasm increases forcing the plasma membraneoutwards against the cell wall. A pressure developscalled the turgor pressure (pressure potential), whichis excerpted against the cell wall. The outwardpressure is matched by an inward pressure, equal inmagnitude but opposite in direction. These pressuresare called turgor pressures and provide mechanicalsupport to the plant tissue. If a plant experiences alack of water the cell becomes plasmolysed, wallpressure is lost and the plant wilts. Normally the outersurface is amenable to matching inward pressure ofinertia (I l lustration 34). But there are manycircumstantial evidences when matching inward wallpressure could get supplemented by some extraforces which affect cellular activity. For instance, turgidpressure in plant cell gets modified on maturity withdecrease in vacuole size (free space) and increase inmass of cytoplasm per unit volume, as shown inIllustration 35, which causes more than usual inwardpressure resulting in narrowing of flow passage. Sucha situation can be explained for increase in pressure ofself gravitation with increase in mass per unit volumewith age. However this is a gap area of investigation.

37. Mechanical loads and centrosome -microtubule organization

Gravitational potential energy is inward and kineticenergy is outward against binding energy. Mechanicalliving cell deformation studies have demonstrated thatmechanical loads are borne by microtubules, whichare balanced by tensile forces in contractile elementsof the cytoskeleton77. Moreover, the disruption ofmicrotubules yields a transfer of forces to theextracellular matrix, a decrease in cell stiffness andaltered cell shape. Evidence also suggests that similarforces that are active on micro-tubules are integral tothe maintenance of nuclear shape and also proposesthat the transfer of mechanical stress across thecytoskeleton may link the alterations in cell andnuclear shape that occur during cell spreading andretraction78, 79. It is interesting to note that in animalcells, the major microtubule-organizing center is thecentrosome, which is located adjacent to thenucleus near the center of interphase (non-dividing)cells. During mitosis, microtubules extend outwardfrom duplicated centrosomes to form the mitoticspindle, which is responsible for the separation anddistribution of chromosomes to daughter cells. Thecentrosome thus plays a key role in determining theintracellular organization of microtubules, althoughmost details of its function remain a mystery. Thusbetween centrosome and microtubule organization, itcan be seen that microtubules in most cells extendoutward from a microtubule-organizing center, in

which the minus ends of microtubules are anchored. Itis apparent that the formation of centrosome isprimarily influenced by potential energy of the selfgravity, whereas microtubule organization isinfluenced by kinetic energy.

Centralized arrangement of microtubules underinverted colour of the photograph taken on usinggreen fluorescent protein (GFP) tagged proteins byJeremy Simpson and Rainer Pepperkok80 arepresented in Illustration 35. Picture demonstratesconclusively the operation of invisible binding energyof self gravity and kinetic energy working against thebinding energy in living cell.

Of late a very interesting question “What determinescell size?”- was sought be answered by group ofindependent researchers81. In the forum article“Physical limits of cell size for embryonic cell divisionin Caenorhabditis elegans”, Akatsuki Kimura pointedout that in transparent C. elegans embryos,centrosomes have the ability to position themselves atthe cell center, enabling the mitotic spindle to positionat the cell center (Illustration 36). The mechanismsmediating centrosome centration may differ amongspecies. Recent studies have supported the idea thatthe cytoplasmic pulling force is a major driving forcefor centrosome centrat ion in animal cel ls.Microtubule-dependent centration of the centrosomemust be facilitated by microtubules, which grow fromthe centrosome and span throughout the cytoplasm tofind the geometrical center of the region. Cell size maybe limited by the physical properties of the cell andpositioning of the mitotic spindle at the cell center iscritical for symmetric cell division. Nothing happenswithout a cause. Potential energy of the self gravitybinds and kinetic energy works against it. Hence thereis need to study invisible central tendency of the forceof self gravity and effect of mutual gravity of twointeracting masses.

38. Inner cell mass (ICM) influences potency instem cells?

Stem cell potency specifies the differentiation potential(the potential to differentiate into different cell types) ofthe stem cell. It can be totipotent, pluripotent,Multipotent, Oligopotent, Unipotent etc. as per theircharacteristics for regeneration or differentiation. Mostinteresting fact is that inner cell mass (ICM) influencespotency in stem cells. For instance, pluripotent,embryonic stem cells originate in inner cell mass (ICM)cells within a blastocyst82. Why inner cell mass orcentral position is an important location asnon-potency stage for regeneration or differentiation instem cells? Compared to periphery, attractivegravitational pull/ force towards core or central position



are higher. Therefore potency for regeneration/differentiation might begin when bio materials aredisplaced from the central position. In central position(at core), potential energy of self gravity is strongest.Metabolic or kinetic energy working against it fails toact in required differential function against the selfgravity while locating itself as inner cell mass. Once itgoes out of the inner cell mass, kinetic energy can setinto motion leading to regeneration or differential ofstem cell. This is similar to an example below. Kineticenergy of a frog for escape can be put to rest onpressing it at central position. On removal of pressurefrom central position, frog can go out to exhibit its fullpotency (Illustration 37). Same is the case for plasmacells8 3 which are large lymphocytes with aconsiderable nucleus-to-cytoplasm ratio. After theprocess of affinity maturation in germinal centers,plasma cells have an indeterminate lifespan, rangingfrom days to months. Recently they have been shownto reside for much longer periods in the bone marrowas long lived plasma cells (LLPC). Thus movementand lifespan of plasma cells depend on location andlocal characteristics within self gravitating environment.

39. Metacenter and floating principle

Under floating condition, locating central position isdependent not only on the mass in question, but alsoon the density of the materials over which such massfloats. For a floating object to be stable, the center ofgravity must be below the center of buoyancy. Themetacenter is a line that intersects both the center ofgravity and the center of mass. The center of gravitymay push the mass downward while the center ofbuoyancy may push the mass upward. When a fish,for example, is being rocked back and forth, center ofgravity and center of buoyancy would come closertogether thus decreasing the metacenter; when centerof buoyancy gets lower than center of gravity, the fishis going to flip (Illustration 38).

40. Neucleus and neucleolus- ‘core’ segment ofthe self gravitating interior

Neucleus and neucleolus under inverted colour of thephotograph taken on using green fluorescent protein(GFP) tagged proteins80 shows that neucleus andneucleolus in vitro condition can be designated as the‘core’ segment of the self gravitating interior of theliving cell (Illustration 39).

41. Change in concentric to eccentric nucleusunder neutral buoyant condition

Deviation from centre or not having same centre isknown as eccentricity. For instance, plasma cells arela rge l ymphocy tes w i th a cons iderab lenucleus-to-cytoplasm ratio. They have basophilic

cytoplasm and an eccentric nucleus84. Why sucheccentric nucleus? Such eccentric nucleus is possibleonly when gravity-buoyancy equilibrium of amacromolecular solid core of nucleus deviates fromthe centre of the inertial frame of reference, as shownin the Illustration 40.

Gravitational attraction provides the restoring forcethat acts to return the eccentric core to its concentricposition. Magnitude of the gravity force is proportionalto the displacement D so long as the density of theouter fluid is constant in the integrated volume and thedensity distribution of the fluid in the remaining part ofthe vessel remains spherically symmetric as well asthe average density of the core and the averagedensity of the ?uid that surrounds the core52. Gravity isthe force that helps to stabilize the central equilibriumposition of the inner macromolecular spherical core.The Archimedes principle provides not valid but onlyan average approximation for the buoyancy force ofcomparatively solid nucleus submerged in cytoplasmicfluid when the size of the nucleus is much smaller thanits distance away from the center of the surroundingmatrix.

42. Prototype of interior dynamics of selfgravitating biomass

Let us draw a prototype84 of the internal gravitationaldynamics of biomass. It has a core of radius R andmass mc bounded by structural membrane and filledwith fluid with a density ρF. The centre of the structureO is the origin of inertial frame of reference anddisplacement of the core D is from the origin. Onorienting system of coordinates along the Z axis thedisplacement of the core could be measured. Thegravitational interaction between the core and the fluidin the interior structure can be determined by thegravitational attraction of the fluid contained inside thestructure of radius R + D (Illustration 41). A paradigmof integration is presented below.

Due to the axial symmetry about the Z axis, only the Zcomponents will contribute to the total force FG.Considering (Illustration 50 Equation 16)

average density of the mass of the spherical core is (Illustration 50 Equation 17) , (Illustration 50 Equation18), (Illustration 50 Equation 19), (Illustration50 Equation 20)

The magnitude of the gravitational attraction is (Illustration 50 Equation 21)

The above result indicates that the magnitude of thegravity force of Mass2 is proportional to thedisplacement D, irrespective of comparative length ofR so long as the density ρF of the fluid remainconstant. When the R occupies the central position (D



= 0) the gravitational force FG = 0 exactly as it was inthe case of the pressure force FP. However, unlike thepressure force FP, for any non-zero value of D theresultant gravity force FG is always oriented towardthe center of the structure O. It means that gravity isthe force that helps to stabilize the central equilibriumposition of the inner spherical core of Mass2. TheArchimedes principle provides not valid but only anaverage approximation for the buoyancy force ofnucleus submerged in surrounding fluid when the sizeof the nucleus is much smaller than its distance awayfrom the center of the surrounding matrix.

Due to compression inside interior of the boundedstructure, hydrostatic pressure increases with depth hfrom the surface according to the relationship: (Illustration 50 Equation 22)

where is density and is the magnitude of theacceleration due to gravity at depth h. The magnitudeof the gravity acceleration g is a known function of theradial distance r measured from the center of thestructure: (Illustration 50 Equation 23)

where G is the gravitational constant. Combining theserelationships (depth and radius of the structure ), (Illustration 50 Equation 24)

where p is the pressure inside the structural interiorand r is the radial distance, a function from the centerof the structure. The expression for the radial pressuregradient is therefore

(Illustration 50 Equation 25)

And since it is negative, it indicates that the pressureincreases with depth for any radial density distributionρ(r). At the core boundary the density of the ?uid is and the pressure gradient is (Illustration 50 Equation26)

where is the average density of the core. Inserting theexpression for gives the buoyancy force forin?nitessimally small D. For a near-concentricspherical core (D ≥ O is the eccentricity), submergedin a spherically symmetric pressure gradient, themagnitude of the buoyancy force (Illustration50 Equation 27)

where R is the radius, is the average density of thecore, is the average density of the fluid that surroundsthe core and is gravitation constant. The negativesign indicates that the buoyancy force FP pushes thestructure away from the maximum pressure point at D= 0 for any D > 0. Therefore such limitations of theArchimedes principle needs to be accounted whilecalculating interactions of self gravity of living masswith planetary gravity considering the situationanalogous to “planet within planet”.

General Property of SelfGravity

43. Self organization due to self gravity

We have already explained that self organization is theintrinsic property of self gravity. Biology cannot beexception, once we recognize the existence of selfgravity in biology. In a glass, of different liquids viz.honey, water, vegetable oil, alcohol can be organizedone above other- thanks to earth’s gravity induceddensity gradient, as illustrated below (Illustration 42).

Similar to aforesaid example of stratification of liquidsin presence of extrinsic gravity, we can draw ahierarchy of biomaterials in a membrane-bound cellunder the influence of self gravity. DNA sequences aretranscribed into RNA and then translated into aminoacid chains; the latter fold spontaneously intofunctional proteins. But genesis of spatial architecture,including how molecules find their proper location incell space, the origins of supramolecular order, cellmorphology are not yet satisfactorily answered1. Thesequence of macromolecules> molecularself-assembly> pushing denser macromoleculesoutward> formation of twin centre of mass withdecrease in mutual attraction can be expressed incoarse grain manner in the following, according totheir timeline of formation.

It is common to see that nucleoid in prokaryote andnucleolis or nucleus in eukaryote- all are made ofswarm of macromolecules. Depending upon thetimeline of formation along other types ofmacromolecules, they would tend to lie in the centralposition due to priority of inward attraction of selfgravity to drag higher molecular weight at the initialstage of cel l growth. Such higher weightmacromolecules subsequently become lighter than theequivalent volume of cytoplasmic fluid due toconcentration of salts, matrix and therefore could floataway to the outward periphery from the centralposition of self gravity due to side thrust generated bythe co-moving denser fluids. At this late stage, densermacromolecules are pushes outward due tohydrostatic or turgor pressure. With the decrease inmutual attraction due to increase in distance, twincentre of mass forms, each exhibiting individualgravitating barrier (Illustration 43).

Energy producing organelles like mitochondria,chloroplast etc., though having a mixture ofmacromolecules having a combination of higher andlower molecular weight tend to remain little away fromcentral position due to their mechanism for production



of energy as a matter of local effect (Illustration 44).Molecular self-assembly or self organization is thedirect as well as indirect consequence of the action ofself gravity.

44. Formation of twin centre of mass on decreasein mutual attraction

The centrosome is called the "microtubule organizingcenter". Centrosomes in animals contain twoorthogonally arranged centrioles. The organelle islocated near the nucleus in the cytoplasm due topotential energy of self gravity. It divides and migratesto opposite poles of the cell during mitosis. Pushing ofdenser macromolecules outward might be due tohydrostatic or turgor pressure develops during courseof time (Illustration 45).

Gravitational force is a function of the radial distancefrom the core. With decrease in mutual attraction, twincentre of mass, as if two gravitating bodies, oneoutside the other’s gravity barrier could be formed.Location of pin-pointed centre of self gravity might bemore defined in animal than in plant cell, where, incase later, effect of sel f gravi ty might beovershadowed by other local forces.

45. Self gravity dictates self organization ofmacromolecules in living cell

Macromolecules are important for various biologicalfunctions. There are four basic kinds of biologicalmacromolecules. These are carbohydrates, lipids,proteins and nucleic acids. These polymers arecomposed of different monomers. But one thing mightget less attention that these macromolecules arehaving different molar mass or molecular weight inaddition to variation in density. Under free floatingcondition, macromolecules having higher molar massor higher density will occupy the core position of selfgravitating body and macromolecules havingintermediate or lesser molecular weight or lesserdensity will remain away from core. That is, ‘higher thedensity- higher would be the attractive force of selfgravity’ or in reverse way ‘lesser the density - lesserwould be the attraction of self gravity’. This is what ishappening in the movement or posit ion ofmacromolecules in the living cells in general, whichtestify that self gravity is operating in the living cellwithout any doubt. Alternative justifications in thisregard are either absent or not elegant and welldesigned.

Let us assume that release of water molecules andpresence of salts and other materials are ensured inthe fluids from carbohydrates, proteins and othersources. Buoyant like forces automatically come intooperation as a consequence of accumulation of fluid to

a particular depth, thereby separating the rest biomassfrom the inertial external gravitational force. Underl i f ted or free f loating condit ion, biologicalmacromolecules having higher molar mass anddensity would be attracted first at the self gravity’score, as higher the mass, higher would be thegravitational attraction. Compared to nucleic acid,molar mass of carbohydrate is less (say, galactose C6

H12O6 is 180 g/mol. The molar mass, density andsolubility of another carbohydrate C12H22O11 is 342.297g/mol, 1.723 g/cm3 and 683.0 g/L respectively. On theother hand, molar mass of water (H2O) is 18 g/mol,sodium chloride (NaCl) - 58.443 g/mol and so on.Density of water is 1g/ml at 40C. So carbohydrates,water, salts possibly play effective primary role as‘metabolically inert infrastructure’ or as foundation overwhich other macromolecules can ballet as perdictation of potential energy of self gravity and kineticenergy of the macromolecules. Under complexadmixture of different macromolecules in variousorganelles, individual effects may not be pronounced.For the time being we are not bringing such admixtureinto our analysis. We left such analysis for the future.

For instance, in case of nucleic acid, molar mass ofDNA fragments etc. is say, 1000–5,000,000 g/mol.Therefore under near free floating condition, nucleicacid which has higher molar mass or molecular weightas well as density, would tend to remain at the centralcore due to attraction of self gravity. It is to be notedthat nucleic acids contain phosphorus, in addition to C,H, N & O. Unlike proteins, nucleic acids contained nosulfur. The DNA polymer is much larger and mayextend up to 2 meters in length. The nucleus is onlyabout 5µm in diameter. The chromosomal DNA ispacked tightly and fit in that small volume. Themolecular weight of double stranded DNA isapproximately 660 x the number of base pairs. Thegenome of E. coli, for instance, contains 4,639,221base pairs. The molecular weight of one E. coligenome, therefore, would be 660 x 4,639,221 =2,840,000,000 g/mole. Molecular weights for the DNAfrom multicellular organisms are commonly 109 orgreater. The DNA from the smallest humanchromosome is over ten times larger than E. coli DNA.Therefore accumulation of nucleic acid under tightlypacked condition at the central position possiblydemonstrates presence of invisible force of self gravitywithout any contradiction.

Proteins, on the other hand, which have intermediatemolar mass or molecular weight as well as beingcomparatively less denser than nucleic acid, wouldremain in intermediate position under free floatingcondit ion as well as under self gravitating



environment. In case of fats and lipids, molar massare also intermediate. But the density of fats and lipidsis less than protein on equal volume basis. So fats andlipids are under duress of self gravity to occupy theperipheral position under ‘free movement’ (free fall)condition. Hence finding of lipids in cell membrane isnot accidental, but a simple instance of comparativelydelayed action of self gravity in attracting less densematerials compared to high dense materials atparticular point of time (Illustration46).

The molecular weight or molar mass and density ofsome amino acid and fatty acid are shown inIllustration 47 as Table 3 for ready reference.

46. Globular protein form and self gravity

It is interesting that protein sphericity is not yet welldefined though many studies are being conducted.Globular shapes, which are close to a sphere, oftencalled spheroproteins, act as enzymes, hormones,transporters of other molecules, stocks of amino acids,and other roles, and they are the most interestingproteins in the design of drugs and understanding oflife phenomenon. Let us extend the idea of self gravitytowards such globular architecture of protein.

A v e r a g e p r o t e i n d e n s i t y i s amolecular-weight-dependent function85. The spatialaverage density of proteins can be considered equalto 1.35 g/cm3 independent of the nature of the proteinand particularly independent of its molecular weight. Itis worthy to mention that proteins are composed ofhydrophobic and hydrophilic amino acids. As far asmolar mass and density are concerned, there is noremarkable difference between hydrophobic andhydrophilic amino acids (Illustration 47 Table 3). Hydrogen bonding between different atoms providesrequired force. However under free floating nativeaqueous environment, hydrophobic amino acids getburied in the core of a protein as ‘communalaggregation’ forming bonding between them, whereashydrophilic amino acids could remain in the boundaryof a protein for interaction with the aqueous solventforming spherical structure. Thus being shielded byhydrophilic amino acids in the aqueous solvent, thehydrophobic amino acid seems to play a crucial role ofsphericity with packing interactions on forming‘communal aggregation’86. This general scenariosometimes gets changed. For example, the proteinmyoglobin87 contains 0.34 gram of iron in 100 grams ofprotein. The atomic weight of iron is 56; thus theminimum molecular weight of myoglobin is (56 ×100)/0.34 = about 16,500. The minimum molecularweight of hemoglobin that contains four atoms of ironis 4 × 16,500 or 66,000. Thus if a protein contains onlyone molecule of one of the amino acids or one atom of

iron, copper, or another element, the minimummolecular weight of the protein or a subunit differs andthereby their behavior in local self gravitatingenvironment may slightly differ.

47. Native conformation, denaturation andrenaturation of protein and self gravity

After proteins get stabilized by hydrogen bonds, asrevealed from above, the strength of dipole momentgets weaker with increase in distance from the centralposition. At that state, potential energy of self gravitygets increase with increase in mass. Therefore gravitygradients in the backbone of the polypeptide chainspossibly tend to fold to a globular conformation at the‘farthest point’ similar to ‘fountain effect’ with ‘centraltendency’, thereby leading to folding in 3-dimensionalsecondary, tertiary or even quaternary structures ofnative conformation.

In this matter, it is worthwhile to note that formation ofnative conformation of protein cannot be based onsimple classical chemical reactions but on a physicalprocess, as can be seen from subsequent ‘denaturation’ and ‘renaturation’ phenomena ofproteins. The reverse process of native state insecondary and tertiary structure of protein is called as‘denaturation’88. For protein ‘denaturation’, there is aneed for application of some external physical stressor making protein thermally unstable possibly to theextent of overcoming gravity barrier of the selfgravitating mass or putting in a compound such as astrong acid or base, a concentrated inorganic salt, anorganic solvent like alcohol or chloroform. This isimportant to note that on short term basis, gravity isweaker than electrostatic force. Gravity works on massat macromolecular level without any time frame.Protein aggregation is therefore a mass basedaggregation (not charge based). Folding starts afterformation of some critical mass that spread up tocertain critical distance (say, 2.8-3.0 A0). Thus there isample scope to doubt that phenomena could bepropelled by the potential energy of self gravity, as itincreases with increase in mass.

Again ‘denaturation’ of protein results in disruption incell activity and possibly can proceed up to cell death.Why cell activity is to be disrupted, or cell death shouldoccur with simple change in physical form, if chemistryis dominating? It is interesting to note that under‘renaturation’89, proteins can regain their native statewhen the denaturing influence is removed. So unlessa universal binding force of self gravity is not broughtinto picture, native state of globular protein(‘naturation’), ‘denaturation’ and again reversing to itsoriginal form of ‘renaturation’ will continue to remainelusive. So it is difficult to ignore invisible force of self



gravity and hence it is gap area of investigation in lifescience.

48. Some exceptions to general rule

Molar mass and density based thumb rule for action ofthe self gravity in organizing macromolecules may beviolated by various local forces operating at particularperiod of formation, especially for proteins, lipids andothers. For instance, hydrogen bonding, ionicinteractions, Van Der Waals forces, and hydrophobicpacking often might disturb the general pattern ofattraction in protein macromolecules. Amyloids90 forinstance, are insoluble fibrous protein aggregatessharing specific structural traits. They arise from atleast 18 inappropriately folded versions of proteins andpolypeptides present naturally in the body. Thesemisfolded structures alter their proper configurationsuch that they erroneously interact with one another orother cell components forming insoluble fibrils. Theyhave been associated with the pathology of more than20 serious human diseases in that, abnormalaccumulation of amyloid fibrils in organs may lead toamyloidosis, and may play a role in variousneurodegenerative disorders. The site specific localenvironments of these proteins are required to bedefined from the point of surrounding medium ormetabolically inert infrastructure, apart from mass,volume and density of the cell or protein. The idea canbe clear from the following facts.

49. Spheroids fibrous protein and self gravity

Though made up of almost same amino acids, theshape of fibrous proteins, often called scleroproteins,look like a long ?lament or rod, and usually serve asinert structural or storage protein. Keratin, collagen,elastin, and fibroin are all scleroproteins. Their role islimited to protection and support, forming connectivetissue, tendons, bone matrices, and muscle fiber. Mostof its polypeptide chain is parallel to a single axis andare often mechanically strong and highly cross-linked.Under classic artefactual cell culture conditions in aflat, rigid petri dish or as per geometry of the contactsurfaces, it remains in elongated position. It couldpossibly withstand the force of self gravity and remainin extended structure. But the behavior of cartilagecells, for instance, could be affected significantly whenthey are organized in 3-D using a micropatterningtechnique and on carefully positioning the cells withinabout 10 microns of each other i.e. nearly the diameterof a cell and about one-fifth the diameter of a humanhair. Though process was observed to be slow or thesize and shape of the cell clumps varied significantly, itis interesting that the cells clump together into "cellspheroids"91. From the above it is clear that spheroidshape could be formed due to potential energy of self

gravity if there is free floating or free fall condition andself gravity is allowed to operate in unperturbedmanner. As potential energy of self gravity andsphericity are two sides of the same coin, we canassume scleroproteins remain an exception only dueto circumstances of local origin. So it could remain inextended structure, unlike compact form i.e it couldpossibly withstand the potential energy of self gravity.Manuel Théry92 while reviewing micropatterning as atool to decipher cell morphogenesis and functions,pointed out that cell microenvironment, especiallypositioning of adjacent cells, location and orientation ofextracellular matrix (ECM) fibres imposes specific‘boundary conditions’ that influence cell architectureand mechanics. The size and stiffness of themicroenvironment limits cell volume and cell spreading.However for geometrical control, only few studies havecombined the soft, deformable substrates as medium.Hence environment that allows the self gravity to workunperturbed needs to be understood in better mannerbefore drawing flat conclusion.

50. Protein folding problem and topologicalproperty

The protein-folding problem was first posed about onehalf-century ago. Structural biology interpretsmolecular level biological mechanisms in terms of thestructures of proteins and other biomolecules. Dill et al 93

made extensive reviews of protein folding problem.Understanding protein-folding "code" involves thequestion of a given string of amino acids lead to aparticular balled-up ("native") structure of a protein. Itis now understood that proteins fold rapidly becauserandom thermal motions causing conformationalchanges leading energetically downhill toward thenative structure, a principle that is captured infunnel-shaped energy landscapes. The energylandscape is constructed by measuring the stabilitiesof folded fragments for a series of overlapping modularrepeats. Each horizontal tier presents the partiallyfolded fragments with the same number of repeats.Proteins denature at high temperatures because there are many states of high energy and fewerstates of low energy, that is, the landscape isfunneled. Thus ultimately folding speed of a protein isto be correlated with a topological property of its nativestructure. Why ultimately we are going to solve theproblem through topological property?

51. Proteins fold on funnel-shaped energylandscapes

Thus we can see that simple classical chemicalreactions based on electrostatic force cannot solve theproblem of protein folding. Albert Einstein thought thatgravity is what happens when space itself is curved or



warped around a mass, such as a star or a planet.Thus, a star or planet would cause kind of a dip inspace so that any other object that came too nearwould tend to fall into the dip. Such curved geometryin spacetime governing the motion of inertial objects isbeing interpreted as gravity mainly generated by themass of an object (Illustration 48 left). On the otherhand, in funnel-shaped energy landscapes protein foldquickly due to random thermal motions causingconformational changes leading energetically downhilltoward the native structure (right). An unfolded proteinstarts out in a state of high free energy that makes itsconformation unstable. However, as the protein startsto fold, the free energy begins to drop and the numberof possible conformations begins to decrease like theshrinking width of a funnel. The bottom of the funnel isreached when free energy is minimized. As the freeenergy drops, however, there may be kinetic trapsalong the way that can stop the folding process andhold the protein in partially folded conformations,known as molten globules and folding intermediates,for extended periods of time. Eventually these trappedconformational states are transformed into a stableconformation but the shape and form of that finalconformation is influenced by the kinetic traps. It is apoint of interest that such kinetic trap and potentialenergy of gravity has any relation. Because we knowthat aqueous solution of protein adopts threedimensional shapes that gives diverse pattern ofprotein folding having different size and shape ofproteins in golf course, moat or other energylandscapes. Moreover varying solution conditions,such as hydration shells across the proteins, salt type,salt concentration, cosolutes, preservatives,surfactants affect this process apart from temperatureand pH. Hence there is a need to study meticulouslythese external factors to ascertain is there is anyuniversality or commonality in astrophysical andbiological worlds. Here principle is important thanminiature size. This is high time to understand whenand where do protein folds, whether with increasingpotential energy of gravity at its central position,proteins are progressively directed towardsincreasingly low energies.

Continued to Part II for more evidences includingconclusion

Under the principle of abductive reasoning throughsuccessive approximation on sporadic set ofobservations, some more evidential roles of selfgravity on identical astrophysical principles of largermass have been conceptualized that are appended inpart II of the present article. We are going to add ourconclusions at the end of the Part II of the article.

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Illustrations

Illustration 1

Illustration 1. Working against self gravity of the Sun was laborious (left) for the Geniewhereas keeping Sun intact (right), the Genie had no work. Self organization is the intrinsicproperty of self gravity.

Illustration 2

Illustration 2. Particle hierarchy and domain of various basic forces in life science shows thatgravitational force becomes dominant force from level of macromolecules at organelles andcontinues up to organism level with accumulation of mass.



Illustration 3

Illustration 3 Table 1

Illustration 4




Illustration 5

Illustration 5 (a,b,c). An egg floats on saline water, on working against earth's gravity, due tobuoyant force (a). Similarly amniotic fluid inside inertial womb/anatomical structure of motheror various ionic fluids secludes fetuses or macromolecules from extrinsic gravity, apart fromother functions as solvent etc. (b, c).

Illustration 6

Illustration 6. Relative three tier reference frame: embryo with metabolic energy (ME)accelerated, fluid or metabolically inert infrastructure (MII) in non-accelerated reference frame,and relevant infrastructures in inertial reference frame.



Illustration 7

Illustration 7ab. a. Relative three tier reference frame for children playing in the runningcompartment of the train: ball is in accelerated reference frame, running compartment of thetrain in non-accelerated reference frame, and wheel upon ground in inertial reference frame; b.Children are playing ball on the stationary ground.

Illustration 8

Illustration 8. Reducing amount of water below 80% of the normal level inhibits metabolism inbrine shrimp23. With inadequate depth of supporting fluids, macromolecular mass in theinterior lost their gravitational seclusion identity.



Illustration 9

Illustration 9. The Pascal’s law invites the presence of entity of two bodies; first one is to dipon the other and pressure by it is to be applied to the enclosed liquid to express in transmittingequally to every part of the liquid. Is it what Harold M Franklin1 prompted to say that “ofcellular morphogenesis … we know much but understand little.”

Illustration 10

Illustration 10. Neutral buoyancy apparently secludes self gravity of macromolecules from theworking of the extrinsic gravity of planet? Measurement of the largest vertical pocket istherefore indispensible for fetal health. Inner purpose of AFI is to track proper seclusion.



Illustration 11

Illustration 11. Pair-wise comparisons of in utero through ultrasound and ex uteromeasurements of CRL and abdominal circumference in mice (reproduced with permissionfrom Junwu Mu et al)32.

Illustration 12

Illustration 12. Kids also imitate playing football by the adult



Illustration 13

Illustration 13. Metabolically inert infrastructure (MII) plays anti (self) gravitational role. Withoutsupport of MII towards opportunity of seclusion from stronger extrinsic gravity, death occurs.

Illustration 14

Illustration 14. Pictures show normal (above left) and diseased (above right) cartilage cellswhich are organized differently in normal and diseased cartilage and 3-D cell clusters of samenormal (middle left) and diseased (middle right) cartilage precisely re-created in a tissue likegel compared to cells (bottom) in a conventional 2-D petri dish. MII or medium helps propersecluded condition for manifestation of self gravitation in living cells.



Illustration 15

Illustration 15. Final cross linked gel structure matrix of agarose allows effective stressdistribution of concentrated gravitational load

Illustration 16

Illustration 16. Why bio-matters are to be positioned over sponge and agarose gel? Sponge aswell as agarose gel provides mechanical rigidity in order to withstand compressibility or bulkmodulus (substance’s resistance) of the stress applied from own weight (effective stress) andfrom external load (net stress). For effective rafting, the biomass is required to be secluded,isolated or free from stress on flotation or through other mechanisms.



Illustration 17

Illustration 17. Biomass is initially to be anchored through inertia of the critical amount ofcallus/ explants, suspension of cultures, or cell density for a three dimensional cell to bepivoted on the central axis of the self gravity. Mitochondria (cellular power plants) remain awayfrom the centre and can then deliver requisite energy for life. ‘Rolling stone gathers nomosses- are not a literary proverb but based on scientific observation of the commoners.

Illustration 18

Illustration 18. Energy producing organelles and mechanisms are away from the centre of selfgravity of a cell or away from the central axis of the reference frame of biomass say, in animal,plant and prokaryotic bacterial cell.



Illustration 19

Illustration 19. Graph shows inverse relationship between metabolic rate and body mass inliving organisms as per Kleiber’s Law.

Illustration 20

Illustration 20. Scaling had been attempted by researchers on small to huge animal todemonstrate mathematical and geometric nature of circulatory networks that distributenutrients and carry away waste and heat56. The bigger the animal, more efficient it usesenergy.



Illustration 21

Illustration 21. During movement of human thoracic diaphragm, potential energy of self gravitycontracts the dome shape structure. The inertia attempts to bring back contracting surface toits original position. Kinetic energy of metabolism works against it, thereby, allowing domeshape structure to relax. Resting metabolic rate (RMR) is involved in such internal activityagainst self gravity.

Illustration 22

Illustration 22.Raising a ball through a height above earth’s surface involves metabolic kineticenergy against potential energy of earth’s gravity as well as spending metabolic energy as perphysical activity level (PAL) on contracting and relaxing muscles.



Illustration 23

Illustration 23. Central position of a gravitating system would be as if the entire mass in thesphere of influence would have been concentrated at that point

Illustration 24

Illustration 24. Nucleoid in prokaryote and nucleolis or nucleus in eukaryote remain in thecentre



Illustration 25

Illustration 25 . Geared elevator system or lift works on a number of engineering principles tocarry load and not on simple switch ‘off’ and ‘on’ of electric motors (left). A rescuer can easilydrag a drowning person in water by holding his hair (right). But same thing is not possible interrestrial environment. In a mechanical system, nervous system of electrical origin cannotregulate transmission of load required for human physical activities.

Illustration 26

Illustration 26. Schematic diagram shows full tone due to balance between potential energy ofself gravity and kinetic energy of metabolism (left). Tone is lost and organism behaves as inertmatter out of imbalance between inner potential and kinetic energies when stronger externalgravity dominates (right).



Illustration 27

Illustration 27. Intuitive schematic diagram showing maintenance of constant angle betweenradius from the common centre and tangents over intercepted arcs from central angle (right)on dome shaped thoracic diaphragm with potential and kinetic energy (left), balloon-like heartat central position and alternate ‘half-bulging’ structure in the skeletal muscles in the peripherywith potential and kinetic energy (middle).

Illustration 28

Illustration 28. In logarithmic spiral (left), tangent to any point on the curve maintains constantangle (in red) with the radius. Magnitude of potential energy of self gravity goes on decreasingfrom centre to the periphery whereas higher magnitude of outward kinetic energy (in yellow)could make radius of curvature lengthened (in blue) leading to logarithmic spiral phenomenain various living creatures like snail (right), snake and others.



Illustration 29

Illustration 29. Low and high frequency could possibly be a differential feature between selfgravitational waves and electrical waves.

Illustration 30

Illustration 30. The peristaltic movement i.e. compression and resultant stretched force orPush-pull travel (P) wave due to inertia and action of the self gravity in longitudinal muscle isapparently available from mouth to stomach, synchronously with circular muscle, consideringstomach and its adjoining areas as the central position and mouth as well as anus as in theperiphery of the self gravitating body.



Illustration 31

Illustration 31. Plasmodesmata and more specifically constriction and openness ofdesmotubule in mesophyll cells of plants is regarded yet an unknown function. Pressure-flowrelationship seems evident in the flow, with increase in self gravitation pressure at strategicsite.

Illustration 32

Illustration 32. Why volume regulations in trafficking route and in overall size of innermacromolecule are important? Why any physical imbalances between the two as regard theirsizes create health hazards? Control of sizes of inner macromolecules may be hydrodynamicbased on tonicity, but what about overall size of the trafficking route? Which factor control sizeof the route? This is a gap area of investigation.



Illustration 33

Illustration 33. Exposure to a hypertonic environment76 (B) results in a reduced nuclear tocytoplasmic ratio, when compared to isotonic culture medium (A) or isotonic normal saline (C).This is indicative that buoyed up force of the fluid can be manipulated within the stipulatedvolume of the cell to get desired size of the nucleus, through process of osmosis anddiffusion.

Illustration 34

Illustration 34. Matching inward pressure that helps to develop adequate turgid pressure inplant cell gets modified with maturity i.e. increase in mass per unit volume.



Illustration 35

Illustration 35. Pictures show centralized arrangement of microtubules (a) taken on usinggreen fluorescent protein (GFP) tagged proteins80 (photos with permission from JeremySimpson and Rainer Pepperkok) and under inverted colour (a’) respectively demonstratingoperation of binding potential energy of self gravity towards centrosomes and kinetic energyagainst binding energy in living cell by microtubules.

Illustration 36

Illustration 36. An image of microtubules in an embryonic cell of C. elegans - astralmicrotubules from the spindle reach the cell cortex81 demonstrates inter-gravitationalattraction between adjacent self gravitating bodies.



Illustration 37

Illustration 37. Transformation of potency in stem cell depends on its removal from inner cellmass where potential energy of self gravity remains higher (left). Kinetic energy of a frog forescape can be put to rest on pressing it at central position. On removal of pressure fromcentral position, frog can go out to exhibit its full potency (right).

Illustration 38

Illustration 38. Metacenter is a line that intersects both the center of gravity (G) and the centerof mass (M). When center of buoyancy (B) gets lower than center of gravity, fish is going to flip.



Illustration 39

Illustration 39. Pictures showing (a) neucleus and (b) neucleolus taken on using greenfluorescent protein (GFP) tagged proteins80 (photos with permission from Jeremy Simpsonand Rainer Pepperkok) and under inverted colour (a’, b’) respectively. Neucleus andneucleolus can be designated as the ‘core’ segment of the self gravitating interior of the livingcell.

Illustration 40

Illustration 40. Sphere of inner macromolecules with centre O’ at reference frame (x’, y’, z)displaced by D from the centre O of the inertial reference frame (x, y, z) under neutral buoyantcondition, making eccentric nucleus from concentric one.





Illustration 41

Illustration 41. Displacement of the core can be measured on orienting system of coordinatesalong the Z axis. The gravitational interaction between the core and the fluid in the interiorstructure can be determined by the gravitational attraction of the fluid contained inside thestructure of radius R + D.

Illustration 42

Illustration 42. Honey, water, vegetable oil and alcohol- all liquids can be organized oneabove other- thanks to earth’s gravity induced density gradient.



Illustration 43

Illustration 43. Hierarchy of biomaterials are shown with the sequence of (i) DNA> (ii) RNA>(iii)Protein> (iv)Macromolecules> (v)Molecular self-assembly> (vi) Pushing densermacromolecules outward> (vii) With decrease in mutual attraction, twin centre of mass forms.

Illustration 44

Illustration 44. Picture showing mitochondria (a) using green fluorescent protein (GFP) taggedproteins80 (photos with permission from Jeremy Simpson and Rainer Pepperkok). Energyproducing organelles mitochondria are little away from central position.



Illustration 45

Illustration 45. Picture showing centrosomes using green fluorescent protein (GFP) taggedproteins80 (photos with permission from Jeremy Simpson and Rainer Pepperkok).Centrosomes migrate to opposite poles of the cell during mitosis, possibly due to outwardhydrostatic/ turgor pressure.

Illustration 46

Illustration 46. Self organization of macromolecules: potential energy of self gravity attractsnucleic acids to cell’s near central position due to highest molar mass and density. Proteinshave intermediate molar mass- thus remain in intermediate position. Fats and lipids are lessdense than others remain in periphery in cell membrane.



Illustration 47


Illustration 48

Illustration 48. As per Einstein, gravity is when space itself is curved or warped around a mass,e.g. star or planet. Inertial object that came too near would tend to fall into the dip of thespacetime curvature (left). Protein fold quickly due to random thermal motions causingconformational changes leading energetically downhill toward the native structure andfunnel-shaped energy landscapes (right).



Illustration 49

Illustration 49 Equation (1) to (15)

Illustration 50

Illustration 50 Equations (16) to (27)



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