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A TOUR OF THE CELL

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Dr.Bhavna Tyagi(PG 1ST year)

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content History Defination of cell Types and difference between prokaryotic and

eukaryotic Cell theory Basic aspect Cell membrane Cytoplasm and its organelles Function of organelles Cytoskeleton Functional system of cell

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Cell cycleMitosis and MeiosisCheckpoints in cell cycle Apoptosis

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history

Robert Hooke used simple lenses to observe cork in which he saw tiny compartments he called cells (cellulae)

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What is a cell?5

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An aggregate of cells in an organism that have similar structure and function :Tissue

an organ (or viscus) is a collection of tissues joined in a structural unit to serve a common function

An organism may be either unicellular (a single cell) or comprise many trillions of cells grouped into specialized tissues and organs.

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Types of cell

1.Prokaryotic cells :nucleus without membrane eg . Bacteria and Blue green algae

2.Eukaryotic cell : organised nucleus and cell organelles eg . Plants and animals

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Difference between prokaryotic and eukaryotic

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CELL THEORY The Cell Theory 1. Schleiden (a botanist) and Schwann (a zoologist): believed that all plants and animals consist of cells. 2. Virchow: cells come from preexisting cells.

The Cell Theory: three generalizations: 1. All organisms are composed of one or more cells. 2. The cell is the smallest unit having the properties of life. 3. The continuity of life arises directly from the growth and division of single cells.

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Basic aspectsStructural Organization of Cell All cells have three basic parts:

• 1. Plasma membrane:- separates each cell from the environment, permits the flow of molecules across the membrane

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• 2. A DNA-containing region occupies a portion of the interior

• 3. The cytoplasm contains membrane-bound compartments (except bacteria), particles, and filament all bathed in a semifluid substance

Continues…

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Cell membrane Biological membrane that separates

the interior of all cells from the outside environment

Selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells.

Protect the cell from its surroundings.

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Thin, pliable, elastic structure

only 7.5 to 10 nm thickComposed entirely of proteins

and lipidsAppears to be trilaminar in

electron microscope.

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Components of membrane

Lipid bilayerCholesterolCarbohydratesProteins

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Fluid mosaic model of membrane 15

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CELL MEMBRANE consist of bilayer of phospholipid molecules that are amphipathic,i.e consist of polar head and nonpolar tail

Polar head

(water loving)

Non polar tail

(water hating)

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PHOSPHO LIPID MOLECULE

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CHOLESTROL MOLECULES

CHOLESTROL MOLECULES are present in the bilayer(1:1 ratio with the phosphate)

Stabilize and regulate the fluidity of the bilayer

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PROTEIN MOLECULES2 types: (a) Integral proteins: Protrude all way through the membrane. Provide structural channels(or pores) through which water molecules and water soluble substances(ions) can diffuse between extracellular and intracellular fluid.

(b) Peripheral protiens: attached to only one surface . No penetration.

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FUNCTIONS OF TRANSMEMBRANE PROTEIN

CELL TO CELL adhesionCELL MATRIX adhesionFormation of pores or channels for the

transport of materials into and out of the cell

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GLYCOCALYX Membrane Carbohydrates

Occur in combination with proteins and lipids in form of glycoproteins or glycolipids.

Entire outside surface of the cell often

has a loose carbohydrate coat called “ glycocalyx”

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Cytoplasm and its organelles

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CYTOPLASM

Material enclosed by plasma membrane.

Clear fluid portion of the cytoplasm in which particles are dispersed is called “cytosol”

Occupies space between plasma membrane and nuclear membrane

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Chemical composition of protoplasm

Water:75 -85% Protein :10-12% Lipid:2-3% Carbohydrates:1% Inorganic substances:1% DNA:0.4% RNA:0.7%

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Types of Organelles

Nonmembranous organelles: no membranedirect contact with cytosol

Membranous organelles: covered with plasma membraneisolated from cytosol

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Membranous Organelles

Endoplasmic reticulum (ER)Golgi apparatusLysosomesPeroxisomesMitochondria

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Non membranous organelles

Ribosomes (free ribosomes and polysomes)Microtubules Centrioles Cilia and flagellaFilaments

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THE NUCLEUS

Discovered by Robert Hooke in 1831

Is the cell’s control center

Contains DNA: genetic material

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The Nucleus contains DNA,protein called as NUCLEOPROTEIN and some RIBONUCLEIC ACID.

2 TYPES OF NUCLEOPROTEIN

HISTONE NON HISTONE

Control the coiling and expression of the genes encoded by DNA strands n NON PROTEIN HISTONES

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NUCLEI are hetrogenous structures with electron-dense(dark) and electron-lucent(light)

HETROCHROMATIN H, consist tightly coiled inactive chromatin found irregular clumps

EUCHROMATIN E, represents that part of the DNA that is active in RNA synthesis

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CHROMATIN –collectively , HETROCHROMATIN and EUCHROMATIN are known as CHROMATIN

CHROMATIN is a highly organised but dynamic structure with the individual chromosome tending to clump in particular areas of the nucleus ,known as chromosome territories

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THE NUCLEOLUS

It is an accumulation of large amount of RNA and proteins.

Nucleolus becomes considerably enlarged

when the cell is actively synthesizing proteins.

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MICROGRAPH OF NUCLEOLUS

F- filamentous component G-granular component The filamentous component

are the site for the ribosomal RNA synthesis

RIBOSOME assembly take place in the granular component

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NUCLEAR ENVELOPE

The Nuclear envelop NE,which encloses the nucleus N,Consist of 2 layers 0f membrane with the INTERMEMBRANOUS or PERINUCLEAR SPACE between

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NUCLEAR PORES

The nuclear envelop contain numerous NUCLEAR PORES (NP) at the margins of which the inner and outer membranes become continuous

NUCLEAR PORES permit and regulate the exchange of metabolities ,macromolecules and ribosomal subunits between the nucleus and cytoplasm

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Endoplasmic Reticulum

This is a complex network or reticulum of membranes running throughout the cytoplasm

Walls are constructed of lipid bilayer membranes that contain large amounts of proteins

Contain of flattened membrane bound sacs called CISTERNAE

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Endoplasmic Reticulum CONT.

Cisternae are storage chambers within membranes

2 types:

Rough endoplasmic reticulum

Smooth endoplasmic reticulum

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ROUGH ENDOPLASMIC RETICULUM

It has ribosomes attached throughout the surface

This type of ER is present in the cell which shows active protein synthesis

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Micrograph shows rER tends to b profuse and to form closely packed laminae of flattened cisternae

NOTE the close association between the rER and the outer lipid bilayer of the nuclear envelop NE with which its in continuity

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Smooth Endoplasmic Reticulum

No ribosomes attached

Tubular Membrane

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Function of sER and eER

Active transport

Forms skeletal

frame work

Metabolic activities due to enzymes

Provide increase

surface area

Formation of new nuclear membrane during cell

division

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Function of sER

GLYCOGEN SYNTHESIS

LIPID AND STEROID SYNTHESIS

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FUNCTION OF rER

Site for protein synthesis

Help in transport of protein

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GOLGI APPARATUS

Golgi apparatus is made up of one or more golgi bodies which are stacks of 3 – 10 flattened sacs and vesicles

Closely related to endoplasmic reticulum

Prominent in secretory cells.

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GOLGI APPARATUS

Vesicles from the endoplasmic reticulum(via the vesicular-tubular clusters) fuse with the network and subsequently progress through the stack to the trans Golgi network, where they are packaged and sent to their destination. Each region contains different enzymes which selectively modify the contents depending on where they reside.

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FUNCTIONS

Formation of cell wallSynthesis of glycolipidLysosomes formationWater balanceLipid secretionProtein secretion

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Lysosome

membrane-bound cell organelle

They are structurally and chemically spherical vesicles containing hydrolitic enzymes

250 to 750 nm in diameter.Surrounded by a typical lipid bilayer membrane.

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Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum.

The enzymes are released from Golgi apparatus in small vesicles which ultimately fuse with acidic vesicles called endosomes, thus becoming full lysosomes

They are popularly referred to as "suicide bags" or "suicide sacs" of the cell

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Types of lysosomes

Primary –these are small vesical like structure produced from the golgi apparatus

Secondary-they are formed when phagosomes fuse with already existing primary lysosomes

Residual bodies Autophagic vacuoles –these lysosomes

envelope and attack intracellular organelles like mitrochondria etc and digest them

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FUNCTIONS

Provide an intracellular digestive system that allows the cell to digest within itself

(a) damaged cellular structures

(b) food particles that have been ingested .

(c) unwanted matter such as bacteria.

Autolysis of a cell by release of the enzymes with in the cell

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Peroxisomes Are enzyme-containing vesicles

Break down fatty acids

Membrane sacs containing oxidases and catalases to neutralize free radicals that are formed during catabolism of organic molecules

Produce hydrogen peroxide (H2O2)

Peroxisomes not made by Golgi apparatus rather formed by self-replication.

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Peroxisomes53

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MITOCHONDRIA

Power house of the cell.

Present in all areas of the cell’s cytoplasm.

Variable in size n shape

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Two lipid bilayer protein membrane: outer and inner membrane.

Many infoldings of inner layer forms shelves onto which oxidative enzymes are attached.

Inner cavity of mitochondria is filled with matrix that contains large quantity of dissolved enzymes that are necessary for extracting energy from nutrients.

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The cytoskeleton

Cytoskeleton: Supporting framework

Three main types : microfilament, microtubules and intermediate filament

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FILAMENTS AND TUBULAR STRUCTURES Microfilaments

Thin filaments (<6nm diameter) Composed of the protein actin Usually at periphery of the cell

Functions:provide additional strength by attaching the membrane

to the cytoplasmAttach integral proteins to cytoskeletonPairs with thick filaments of myosin for muscle

movement

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Intermediate Filaments & Thick Filaments Intermediate Filaments:

7-11 nm diameter

Mid-sized between microfilaments and thick filaments

Durable, type varies with cell

Functions:

• strengthen cell and maintain shape

• stabilize position of organelles

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Thick Filaments

15 nm diameter Composed of myosin Muscle cells only

FunctionInteract with actin to produce movement

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Microtubules

Large (25nm diameter), hollow tubes

Composed of tubulin protein

Originate from centrosome

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Functions Foundation of the cytoskeleton

Allows the cell to change shape and assists in mobility

Involved in transport

Makes up the spindle apparatus for nuclear division (mitosis)

The structural part of some organelles

Centrioles, cilia, flagella

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Centrioles in the Centrosome

Centrioles : form spindle apparatus during cell division

Centrosome: cytoplasm surrounding centriole near the nucleus Consists of matrix and paired centrioles

Responsible for assembling spindle apparatus during mitosis

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Cilia and Flagella

Hair like projections

Contain a microtubule core with cytoplasm covered in plasma membrane

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Cilia: Short, numerousFunction: sweep substances over cell surface

Flagella: Long, singularFunction: propel cell through environment

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FUNCTIONAL SYSTEMS OF THE CELL Ingestion by the cell – ENDOCYTOSIS The plasma membrane envelops small

particles or fluid, then seals on itself to form a vesicle or vacuole which enters the cell: Phagocytosis Pinocytosis Receptor-Mediated Endocytosis

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Phagocytosis (cell eating)

In phagocytosis, a cell engulfs a particle by Wrapping pseudopodia around it and packaging it within a membrane enclosed sac large enough to be classified as a vacuole called as phagosomes

The particle is digested after the vacuole fuses with a lysosome containing hydrolytic enzymes.

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phagocytosis 67

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Pinocytosis (cell drinking) Endosomes “drink” extracellular fluid

and enclose it in membranous vesicles at the cell surface

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Mitosis and MeiosisCell cycleCheckpoints in cell cycle ApoptosisThese topic will be cover in next seminar

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Bibliography : wheater’s functional histology . A text

and colour Atalas . fifth edition Arthur C. Guyton; John E. Hall. Text

book of Medical Physiology. Tenth edition.

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THANK YOU

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Cell cycle and replication

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cell cycleProliferating cell progress

through a series of checkpoints and defined phases called THE CELL CYCLE

CELL CYCLE consists of G1,S,G2,M,G0 phases

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CELL CYCLE

cell growth, organelle duplication, protein synthesis, synthesizes enough cytoplasm for 2 cells

DNA replication and histone synthesis.8-12 hours after mitosis and 7-8 hrs for completion.

finishes protein synthesis and centriole replication

Mitosis involves division of the chromosomes. Cytokinesis involves division of the cytoplasm.

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Cell division

Multiplication of cells takes place by division of pre-existing cells.

Body (somatic) cells divide in 3 stages:

DNA replication duplicates genetic material exactly

Mitosis divides genetic material equally

Cytokinesis divides cytoplasm and organelles into 2 daughter cells

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Mitosis

What is the purpose of mitosis?

Cell division

Products genetically identical

Growth of organism

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Stages

The period during which the cell is actively dividing is the phase of mitosis

The period between two successive divisions is called the interphase

Interphase is often included in discussions of mitosis, but interphase is technically not part of mitosis, but rather encompasses stages G1, S, and G2 of the cell cycle.

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Divided into

Prophase

Metaphase

Anaphase

Telophase

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Interphase The cell is engaged in metabolic activity and performing its prepare for mitosis (the next four phases that lead up to and include nuclear division).

Chromosomes are not clearly discerned in the nucleus, although a dark spot called the nucleolus may be visible.

The cell may contain a pair of centrioles (or microtubule organizing centers in plants) both of which are organizational sites for microtubules.

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prophase Chromatin in the nucleus begins to condense and becomes visible in the light microscope as chromosomes.

The nucleolus disappears.

Centrioles begin moving to opposite ends of the cell and fibers extend from the centromeres.

Some fibers cross the cell to form the mitotic spindle.

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Prometaphase The nuclear membrane dissolves, marking the beginning of prometaphase.

Proteins attach to the centromeres creating the kinetochores.

Microtubules attach at the kinetochores and the chromosomes begin moving.

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Metaphase Spindle fibers line the

chromosomes along the middle of the cell nucleus. This line is referred to as the metaphase plate.

Polar microtubules extend from the pole to the equator, and typically overlap

Kinetochore microtubules extend from the pole to the kinetochores

This organization helps to ensure that in the next phase, when the chromosomes are separated, each new nucleus will receive one copy of each chromosome

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Anaphase The paired chromosomes separate at the kinetochores and move to opposite sides of the cell.

The chromosomes are pulled by the kinetochore microtubules to the poles and form a "V" shape

Motion results from a combination of kinetochore movement along the spindle microtubules and through the physical interaction of polar microtubules.

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Telophase Chromatids arrive at opposite poles of cell, and new membranes form around the daughter nuclei.

The chromosomes disperse and are no longer visible under the light microscope.

The spindle fibers disperse, and cytokinesis will start

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Cytokinesis In animal cells, cytokinesis results when a fiber ring composed of a protein called actin around the center of the cell contracts pinching the cell into two daughter cells, each with one nucleus.

In plant cells, synthesis of new cell wall between two daughter cells rather than cleavage furrow in cytoplasm

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Meiosis

FunctionReduction division (23 chromosomes per gamete)

MechanismEach homologue (e.g. “chromosome 7”)

replicates to give two sister chromatids

Homologues pair (e.g. maternal chromosome 7 and paternal chromosome 7)

Exchange of material between non-sister chromatids: crossing-over, recombination

Chiasmata (visible cytologically) are the physical manifestations of crossing-over

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Meiosis IntroductionMeiosis consist s of two successive

divisions called the first and the second meiotic divisions

1st meiotic division

Prophase is prolonged

Divided into 4 stages

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Meiosis I Fig A represents leptotene stage-chromosomes become visible consist 2 chromatids ,cnt distinguish

Fig B represents zygotene stage-pairing of chromosome called synapsisThe two chromosomes together c/a bivalent

Fig C represents pachytene stage -4 chromatid visible c/a tetrads,2 central and 2 peripheral chromatids.Cont..

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Fig D cont. pachytene stage-2 central chromatid cross over c/a crossing overThe point of crossing c/a chiasmata

Fig E represents Diplotene stage-2 chromosomes of a bivalent try to move apart Exchange of genetic material occur

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Nuclear membrane disappear Spindle has formedChromosomes attach to the spindle at equatorChromosome attach by centromere

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One entire chromosome of the pair moves to either poleNOTE that the centromere does not divide

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Similar to mitosisNOTE that the chromosome in each cell have been reduced to half the diploid number

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2nd mitotic division

The 1st mitotic division is follow by the short interphase

There is no duplication of DNA

2nd meiotic division similar to the mitosis

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Regulation of cell cycle

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Nuclear transcription factor

Quiescent cell receive a signal to divide

MYC protein binds to DNA

Transcriptional activation of several growth related genes including cyclin dependent kinases

Drive cell into cell cycle MYC decline

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Cyclins and Cyclins –Dependent Kinases

Phosphorylation of RB, molecular on off switch

G2/M transition initiated by E2F mediated transcription of cycline A,which form complex cycA cdk2 tht regulates mitotic prophase

Main mediator tht propel the cell beyond prophase is cyc B-cdk1 complex .activation of complex leds to breakdown of nuclear envelop n initiates mitosis

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Cell cycle inhibitor

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cell cycle check points

Cell cycle has its own internal control called as checkpoints

2 main check points ,1 at G1/M transition and another at G2/M

S phase is point of no return ,before cell makes the final commitment to replicate ,G1/S checkpoint checks for DNA damage

DNA damage after its replication can still be repaired as long as the chromatids have not separated .the G2/M checkpoint monitor the completion of DNA replication and checks whether the cell can safely initiates mitosis and separates sister chromatids

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G1/S checkpoint , cell cycle arrest is mostly mediated through p53,which induce cell cycle inhibitor p21

Arrest of cell cycle by G2/M checkpoints involve the both p53 dependent via cyclin A/cdk-2 and independent via cdc 25 mechanism

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p53 Also called as “guardian of the genome”

Present on chromosome 17

Most mutated gene in human cancer p53 links cell damage with DNA repair ,cell cycle arrest and apoptosis.

P53 links cell damage with DNA repair ,cell cycle arrest and apoptosis

In reponse to DNA damage,it is phosphorylated by gene that sense the damage and are involved in DNA repair

P53 assist in DNA repair by causing G1 arrest and inducing DNA repair

A cell with DNA damaged tht cant be repaired is directed by p53 to undergo apoptosis

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Regulation of cell cycle

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APOPTOSIS PROGRAMMED CELL DEATH

It is a pathway of cell death that is introduced by a tightly regulated suicide program in which cells destined to die activate enzymes that degrade the cell’s own nuclear DNA and nuclear and cytoplasmic proteins.

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(a) In phisiologic conditions:

Normal phenomenon that serves to eliminate cells that are no longer needed and to maintain a steady number of various cell populations in tissues.

examples:

During embryogenesis.

Involution of hormone-dependent tissues upon hormone withdrawal.

Cell loss in proliferating cell populations , such as immature lymphocytes in the bone marrow and thymus .

causes

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In pathological conditions: Eliminates cells that are injured beyond repair

without eliciting a host reaction, thus limiting collateral tissue damage.

DNA damage: radiation anticancer drugs and hypoxia.

Accumulation of mis folded proteins- because of mutations in the genes encoding these proteins or damage caused by free radicals.

Viral infections like HIV

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MECHANISM

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Regulation

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Bibliography :

(1)Robbins and Cotran : Pathologic basis of disease: seventh edition

(2)Gobind Rai Garg Sparsh Gupta :Review of pathology and genetics :fifth edition

(3) Inderbir singh :Human Embryology : seventh edition