Biophysik der Zelle Physik der Lipide. hydrophobe Wechselwirkung kritische Mizellkonzentration Permeabilität Diffusion

Transkript

1 Biophysik der Zelle Physik der Lipide hydrophobe Wechselwirkung kritische Mizellkonzentration Permeabilität Diffusion

2 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 Sackmann Skript: Kapitel Membranen

3 Fluid-Mosaic Model Nicholson & Singer 1977 Proteins diffuse freely in a fluid matrix of lipid

4 Lipid membranes as composite materials

5 The structure of the spectrin network

6 Lipide

7 Due to the amphipathic nature of phospholipids, these molecules spontaneously assemble to form closed bilayers

8 Phospholipid structure

9 Bilder Membranes

10 Cholesterol

11 Fettsäuren Name Trivialname Struktur Anzahl der C-Atome A n z a h l d e r ungesättigten Bindungen n - Tetradekansäure Myristinsäure CH 3 (CH 2 ) 12 COOH 14 0 n - Hexadekansäure Palmitinsäure CH 3 (CH 2 ) 14 COOH 16 0 n - Octadekansäure Stearinsäure CH 3 (CH 2 ) 16 COOH 18 0 n - Eicodekansäure Archinsäure CH 3 (CH 2 ) 18 COOH 20 0 Oleinsäure CH 3 (CH 2 ) 7 CH=CH(CH 2 ) 7 -COOH 18 1 Linolsäure CH 3 (CH 2 ) 4 CH=CHCH 2 CH= CH(CH 2 ) 7 COOH 18 2

12 Nomenclature DMPC: DPPC: DSPC: Dimyristoyl-Phosphatidyl-Cholin Dipalmitoyl-Phosphatidyl-Cholin Distearoyl-Phosphatidyl-Cholin

13 Amphiphile Moleküle assoziieren zu Aggregaten Lipid-Monolagen Mizelle Seifenfilm Lipid-Doppelschicht

14 Solubility and partitition function

15 Thermodynamics of lipid aggregation The critical micelle concentration, where further addition of solute molecules result in the formation of more aggregates, while leaving the momomer concentration constant.

16 The hydrophobic effect

17 Morphologien von Lipidaggregaten Mizelle Stäbchenmizelle Bilayer Vesikel Invertierte Mizelle

18 The Packing-Parameter V: Volume a 0 : cross section of headgroup l: alcyl chain length

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20 The Tanford Modell of opposing forces

21 Pulling a single lipid out of a membrane Die Entbindungskraft ist für PC-C14:0 f* 12 pn. Das entspricht einer Bindungsenergie pro Molekül von Δg*~5 k B T die ein Faktor 5 kleiner ist als nach dem hydrophoben Effekt erwartet.

22 H. Grubmüller, Göttingen

23 Force fields

24 Lipid bilayer consisting of 512 POPC lipids. Grubmüller group, MPI Göttingen

25 Efficient, robust and tunable solvent-free bilayer model Ira R. Cooke, Kurt Kremer, and Markus Deserno PHYSICAL REVIEW E 72,

26 Outcome of physical parameters: Observables Diffusion constant orientational order parameter flip-flop rate bending modulus compressibility modulus rupture tension

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29 TRANSPORT

30 A pure phospholipid bilayer acts as a selectively permeable barrier

31 Diffusive flux across a membrane

32 Flux across an energy barrier

33 Transepithelial movement of glucose and amino acids requires multiple transport proteins

34 Six ways in which membrane proteins associate with the lipid bilayer. Most trans-membrane proteins are thought 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 cytoplasmic monolayer (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 an oligosaccharide, 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).

35 Overview of membrane transport proteins

36 Muscle Ca 2+ ATPase pumps Ca 2+ ions from the cytosol into the sarcoplasmic reticulum

37 Na + /K + ATPase maintains the intracellular Na + and K + concentrations in animal cells Sackmann script

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

39 Aquaporin Chemistry Nobel Prize 2003 Peter Agre Die Wasserleitfähigkeit eines Aquaporinkanals beträgt bis zu 3 Milliarden Moleküle pro Sekunde.

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

42 Real time molecular dynamics simulation Aquaglyceroporin tetramer (blue, cyan, orange, magenta), embedded within a POPE lipid 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 (left and middle panels, surface and ribbon representation of the same protein structure) and hydrogen bond energies per water molecule (right). The permeation event shown on the left lasted 3.3 ns.

43 Molecular Dynamics of lipid bilayers

44 Random walks

45 from

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47 Snap shots

48 Mobility in the plasma membrane Jacobson, et al. Science 268 (1995) 5216