Physik der Lipide · 30.04.2008 Physik der Lipide hydrophobe Wechselwirkung kritische...

30.04.2008Physik der Lipide

hydrophobe Wechselwirkung kritische MizellkonzentrationPermeabilitätDiffusion

Biophysik der Zelle

Inhalt• The structure of the plasma membrane• Biochemistry of lipids• Hydrophobic effect, • Micelle formation• Packing Parameter and Tanford Modell• Transport across membranes• Diffusion in membranes

Literatur:„Structure and Dynamics of Membranes“, Sackmann, Lipowsky editors, Springer„Life-as a Matter of Fat“, O. Mouritsen, Springer 2005„Intermolecular & Surface Forces“, Israelachvili, Acad.Press, 2nd Ed. 2005Sackmann Skript: Kapitel Membranen

Fluid-Mosaic Model

Nicholson& Singer 1977

Proteins diffuse freelyin a fluid matrix of lipid

Lipid membranes ascomposite materials

The structure of the spectrin network

Lipide

Due to the amphipathic nature of phospholipids,these molecules spontaneously assemble to formclosed bilayers

Phospholipid structure

Bilder Membranes

Cholesterol

Fettsäuren

218CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH

Linolsäure

118CH3(CH2)7CH=CH(CH2)7

-COOHOleinsäure

020CH3(CH2)18COOHArchinsäuren -Eicodekansäure

018CH3(CH2)16COOHStearinsäuren -Octadekansäure

016CH3(CH2)14COOHPalmitinsäuren -Hexadekansäure

014CH3(CH2)12COOHMyristinsäuren -Tetradekansäure

A n z a h l d e rungesättigtenBindungen

Anzahl derC-Atome

StrukturTrivialnameName

Nomenclature

DMPC: Dimyristoyl-Phosphatidyl-Cholin

DPPC: Dipalmitoyl-Phosphatidyl-Cholin

DSPC: Distearoyl-Phosphatidyl-Cholin

Amphiphile Moleküle assoziieren zu Aggregaten

Lipid-Monolagen

Seifenfilm

Mizelle

Lipid-Doppelschicht

Solubility and partitition function

The critical micelle concentration, where further addition of solute moleculesresult in the formation of more aggregates, while leaving the momomerconcentration constant.

Thermodynamics of lipid aggregation

The hydrophobic effect

Morphologien von Lipidaggregaten

Mizelle

Stäbchenmizelle

Vesikel

Invertierte Mizelle

Bilayer

V: Volumea0: cross section of headgroupl: alcyl chain length

The Packing-Parameter

The Tanford Modell of opposing forces

Pulling a single lipid out of a membrane

Die Entbindungskraft ist für PC-C14:0 f*≈ 12 pN. Das entspricht einer Bindungsenergiepro Molekül von Δg*~5 kBT die ein Faktor 5 kleiner ist als nach dem hydrophobenEffekt erwartet.

H. Grubmüller, Göttingen

Forcefields

Lipid bilayer consisting of 512 POPC lipids.

Grubmüller group, MPI Göttingen

Efficient, robust and tunable solvent-free bilayer modelIra R. Cooke, Kurt Kremer, and Markus DesernoPHYSICAL REVIEW E 72, 011506 2005

Outcome of physical parameters: Observables

• Diffusion constant• orientational order parameter• flip-flop rate• bending modulus• compressibility modulus• rupture tension

TRANSPORT

A pure phospholipid bilayer acts as a selectivelypermeable barrier

Diffusive flux across a membrane

Flux across an energy barrier

Transepithelial movement of glucose and amino acidsrequires multiple transport proteins

Six ways in which membrane proteins associate with the lipid bilayer. Most trans-membrane proteins arethought to extend across the bilayer as a single α helix (1) or as multiple α helices (2); some of these"single-pass" and "multipass" proteins have a covalently attached fatty acid chain inserted in the cytoplasmicmonolayer (1). Other membrane proteins are attached to the bilayer solely by a covalently attached lipid -either a fatty acid chain or prenyl group - in the cytoplasmic monolayer (3) or, less often, via anoligosaccharide, to a minor phospholipid, phosphatidylinositol, in the noncytoplasmic monolayer (4). Finally,many proteins are attached to the membrane only by noncovalent interactions with other membrane proteins(5) and (6).

Overview of membrane transport proteins

Muscle Ca2+ ATPase pumps Ca2+ ions from thecytosol into the sarcoplasmic reticulum

Na+/K+ ATPase maintains the intracellular Na+ and K+

concentrations in animal cells

Sackmann script

Proposed model for operation of the two-Na+/one-glucose symporter

Aquaporin

http://www.mpibpc.gwdg.de/abteilungen/071/bgroot/gallery.html

Chemistry Nobel Prize 2003

Die Wasserleitfähigkeit eines Aquaporinkanals beträgt bis zu 3 Milliarden Moleküle pro Sekunde.

Peter Agre

Aquaporin-1 in action. Simulation fragment of 200 ps of aquaporin-1. Generated using Molscript/Bobscript and raster3d.

„Real time“ moleculardynamics simulation

Aquaglyceroporin tetramer (blue, cyan, orange, magenta), embedded within a POPElipid bilayer(yellow head groups and green tails) surrounded by water (red,white).The total system consists of about 101,000 atoms.

Overlaid snapshots from a trajectory of a water molecule passing through AQP1 (leftand middle panels, surface and ribbon representation of the same protein structure)and hydrogen bond energies per water molecule (right). The permeation eventshown on the left lasted 3.3 ns.

Molecular Dynamics of lipid bilayers

Random walks

from

Snap shots

Mobility in the plasma membrane

Jacobson, et al. Science 268 (1995) 5216