BC368 Biochemistry of the Cell II

1. BC368Biochemistry of the Cell II Biological Membranes Chapter 11: Part 1 February 11, 2014

2. Plasma Membrane “Possibly the decisive step [in the origin of life] was the formation of the first cell, in which chain molecules were enclosed by a semi-permeable membrane which kept them together but let their food in.” J. B. S. Haldane, 1954

3. Plasma Membrane

4. Plasma Membrane Membrane is composed of: • Lipids • Phospholipids • Sterols • B. Proteins • Integral • Peripheral • C. Carbohydrates • Glycolipids • Glycoproteins

5. Plasma Membrane • Variable components in different membrane types

6. Membrane Lipids • Amphiphilic lipids • Major types: phospholipids, glycolipids, sterols sphingosine Glycolipid glycerophospholipid sphingolipid

7. Phospholipids • Two classes: glycerophospholipids (aka phosphoglycerides) and sphingolipids Fig 10-7

8. Membrane Lipids: 1A. Glycerophospholipids • Two fatty acids and a polar “head group” on glycerol. • Vary in the FA’s and head group.

9. Membrane Lipids: 1B. Sphingolipids • Named for the enigmatic Sphinx • Common in nerve and brain cell membranes

10. note amide linkage Membrane Lipids: 1B. Sphingolipids • Named for the enigmatic Sphinx • Sphingosine replaces glycerol, so only 1 FA tail

11. Membrane Lipids: 1B. Sphingolipids • Example: sphingomyelin

12. Glycolipids • Two classes: glycosphingolipids and galactolipids Fig 10-7

13. Membrane Lipids: 2A. Glycosphingolipids • Sphingolipids with carbohydrate head group; common on cell surfaces • Examples: cerebrosides and gangliosides

14. Membrane Lipids: 2B. Galactolipids • Diglycerides with galatose groups • Common in plant (thylakoid) membranes

15. Membrane Lipids: 3. Sterols • Cholesterol and cholesterol-like compounds

16. Lipid Components of Membranes • Lipid composition varies across different membranes. Fig 11-2

17. Turnover of Membrane Lipids Fig 10-16

18. Defects in Membrane Turnover Deposits of gangliosides in Tay Sachs brain

19. Lipid Aggregates • Lipids spontaneously aggregate in water as a result of the Hydrophobic Effect.

20. Lipid Aggregates • Amphiphilic lipids form structures that solvate their head groups and keep their hydrophobic tails away from water. • Above the critical micelle concentration, single-tailed lipids form micelles. Fig 11-4

21. Lipid Aggregates Fig 11-4 • Double-tailed lipids form bilayers, the basis of cell membranes. • Bilayers can form vesicles enclosing an aqueous cavity (liposomes). Fig 11-4

22. Lipid Components of Membranes • Different types of membranes have characteristic lipid compositions.

23. Lipid Components of Membranes • Lipid composition varies across the two leaflets of the same membrane.

24. Membrane Proteins • Integral proteins (includes lipid-linked): need detergents to remove • Peripheralproteins: removed by salt, pH changes • Amphitropicproteins: sometimes attached, sometimes not

25. Single Transmembrane Segment Proteins • Usually alpha-helical, ~20-25 residues, mostly nonpolar. • Example: glycophorin of the erythrocyte. Fig 11-8

26. Multiple Transmembrane Segment Proteins • 7 alpha-helix motif is very common. • Example: bacteriorhodopsin Fig 11-10

27. Beta Barrel Transmembrane Proteins • Multiple transmembrane segments form β sheets that line a cylinder. • Example: porins.

28. Lipid-Linked Membrane Proteins • Attached lipid provides a hydrophobic anchor. Fig. 11-14 • An important lipid anchor is GPI (glycosylated phosphatidylinositol.

29. Membrane Carbohydrates • On exoplasmic face only

30. Membrane Carbohydrates • On exoplasmic face only • An example is the blood group antigens

31. Membrane Dynamics • At its transition temperature (TM), the bilayer goes from an ordered crystalline state to an a disordered fluid one. Fig 11-16

32. Membrane Dynamics • Phospholipids in a bilayer have free lateral diffusion. Fig 11-17

33. Membrane Dynamics • Phospholipids in a bilayer have restricted movement between the two faces. Fig 11-17

34. Membrane Dynamics • Flippases, floppases, and scramblases catalyze movement between the two faces.

35. Fluid Mosaic

36. Fluorescent Recovery After Photobleaching • Fluorescent tag is attached to a membrane component (lipid, protein, or carbohydrate). • Fluorescence is bleached with a laser. • Recovery is monitored over time.

37. Fluorescent Recovery After Photobleaching FRAP Movie

38. Protein Mobility in the Membrane • Some membrane proteins have restricted movement. • May be anchored to internal structures (e.g., glycophorin is tethered to spectrin). Fig. 11-20

39. Protein Mobility in the Membrane • Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins. • Thicker and less fluid than neighboring domains. Fig. 11-21

40. Protein Mobility in the Membrane • Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins. • Thicker and less fluid than neighboring domains. Lipid Rafts

41. Nature Reviews Molecular Cell Biology 4, 414-418 (May 2003) Domains of gel/fluid lipid segregation in a model membrane vesicle, which is a mixture of fluid dilaurylphosphatidylcholine phospholipids with short, disordered chains and gel dipalmitoylphosphatidylcholine phospholipids with long, ordered chains. A red fluorescent lipid analogue (DiIC18) partitions into the more ordered lipids, whereas a green fluorescent lipid analogue (BODIY PC) partitions into domains of more fluid lipids. These domains in a model membrane are much larger than the domains of cell membranes.

42. Membrane Permeability • Membranes are selectively permeable. • Permeable to nonpolars and small polar molecules. • Impermeable to ions and large polar molecules.

43. Membrane Permeability • What actually gets across a membrane depends on several factors: • Solubility in the nonpolar lipid environment • The concentration gradient • Whether a protein transporter exists