1. Biological Membranes

2. Biological Membranes
Organized assemblies of lipids, proteins and small amounts of carbohydrates
Regulate composition of intracellular medium by controlling flow of nutrients, waste products, ions, etc. in and out of cell
Scaffolding
Oxidative phosphorylation
Photosynthesis
Nerve impulses
Hormone receptors
Organelle Membranes

3. Membranes are incredibly complicated structures, with many different components.

4. Types of Membrane Lipids
Glycerophospholipids
Sphingolipids
Cholesterol

5. Membrane Glycerophospholipids

6. Sphingolipids (Sphingomyelin)

7. Cholesterol

8. Amphiphilicity

9. Properties of Lipid Aggregates
Micelles, Liposomes, and Bilayers
Driving Force = Hydrophobic Effect

10. Van der Waals Envelope (Fatty Acids)
Figure 9-13a

11. Micelle (single-tailed lipids)

12. Cylindrical Lipids Individual lipids are cylindrical
-cross-section of head = tail

13. Liposomes

14. Electron Micrograph of Liposome
Figure 9-15

15. Properties/Uses of Liposomes
Single Bilayer
(inner and outer leaflets)
Delivery of Therapeutic Agents
Stable — purification
Manipulate internal content
Delivery — fusion with plasma membrane

16. Bilayer Formation by Phospholipids
Aqueous phase
Aqueous phase

17. Membrane composition

18. Phase Transition in a Lipid Bilayer (Transition Temperature)
Figure 9-18

19. Transition Temperature =more Rigid; =more fluid
Increases with chain length
Tm = more rigid
Increases with degree of saturation
More saturated = more rigid
Cholesterol decreases membrane fluidity

20. Membrane composition Which of these might be the most rigid?
Which one the most fluid?

21. Which membrane composition is more rigid?
Average Chain length
16.0
17.0
Ratio
Unsaturated:Saturated
Fatty acids
2.0
0.5 B
[Adaptation by fish and animals] and bacteria

22. Asymmetry within Membranes

23. Lipid Diffusion in Membranes

24. Transverse Diffusion
Figure 9-16a

25. Flippase/Floppase/Scramblase

26. Lateral Diffusion Which we will get to more in a few minutes.
Figure 9-16b

27. Permeability of Lipid Bilayer
Semi-permeable
Hydrophilic molecules
Non-permeable
Facilitated diffusion
Active transport
Hydrophobic molecules
Permeable
Simple diffusion

28. Membrane Carbohydrates
Mostly oligosaccharides
Variety of sugars
Glycolipids
Glycoproteins
Glycoprotein

29. Peripheral or Extrinsic Proteins Integral or Intrinsic Proteins
Membrane Proteins
Peripheral or Extrinsic Proteins
Integral or Intrinsic Proteins

30. Peripheral or Extrinsic Proteins
Easily dissociated
High ionic strength
pH changes
Free of attached lipid
Water-soluble
(e.g. cytochrome c)
Normal amino acid composition

31. Integral or Intrinsic Proteins
Not easily dissociated or solubilized
Detergents
Chaotropic agents — disrupt water structure
Retain associated lipid
>average hydrophobic amino acds
Significant number hydrophilic amino acds
Asymmetrically oriented amphiphiles
Trans-membrane proteins

32. Integral Membrane proteins
Single transmembrane domain
Multple transmembrane domains
Lipid Linked

33. Lipid Linked Proteins
Lipid linked are sometimes grouped into each category, all the protein is outside the bilayer, but they are strongly attached to th

34. Prenylated Proteins
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35. Prenylated Proteins
Page 268

36. Glycosylphosphatidylinositol (GPI) Linked Proteins

37. Core Structure of the GPI Anchors of Proteins
Figure 9-24

38. Composition of Biological Membranes (protein-lipid ratios)
Myelin ~0.23
Eukaryotic plasma membrane ~1.0
(50% protein and 50% lipid)
Mitochondrial inner membrane ~3.2

39. Asymmetric Orientation

40. Detecting Asymmetric Orientation of Membrane Proteins
Surface Labeling
Proteases

41. Transmembrane Proteins
May contain -Helices
(and -Sheets)

42. Human Erythrocyte Glycophorin A
Figure 9-20

43. Identification of Glycophorin A’s Transmembrane Domain
Figure 9-21

44. Structure of Bacteriorhodopsin
Figure 9-22

45. X-Ray Structure of E. coli OmpF Porin
Figure 9-23a

46. X-Ray Structure of E. coli OmpF Porin Trimer
Figure 9-23b

47. Functions of Membrane Proteins
Catalysis of chemical reactions
Transport of nutrients and waste products
Signaling

48. Hydrophillic compounds need help

49. Glucose transporter

50. Plasma Membrane Structure Fluid Mosaic Model
Figure 9-25

51. Evidence for Mobility of Membrane Proteins

52. Fusion of Mouse and Human Cells
Figure 9-26 part 1

53. Mixing of Human and Mouse Membrane Proteins
Figure 9-26 part 2

54. Fluoresence Recovery after Photobleaching (FRAP) Technique
Figure 9-27a

55. Fluoresence Recovery after Photobleaching (FRAP) Results
Figure 9-27b

56. Distribution of Membrane Phospholipids

57. Distribution of Membrane Phospholipids in Human Erythrocyte Membrane
Figure 9-32

58. Reaction of TNBS with Membrane Surface Phosphatidylethanolamine
Figure 9-33

59. Location of Lipid Synthesis in a Bacterial Membrane
Figure 9-34

60. Redistribution of Membrane Lipids
Flipases
Phospholipid Translocases (ATP-dependent active transport)

61. Distribution of Membrane Phospholipids in Human Erythrocyte Membrane
Figure 9-32

62. Exposure of Phosphatidylserine
Blood clotting (tissue damage)
Removal from circulation (erythrocytes)

63. Membrane Subdomains Basolateral Cells Microdomains Lipid Rafts
Two sided cells
Microdomains
Concentration of specific lipids with specific proteins
Cardiolipin and the electron transport chain
Lipid Rafts

64. Basolateral Cells Asymmetric cell
Active transport of glucose (against a concentration gradient) from intestinal lumen to cytosol
Mediated uniport of glucose (down a concentration gradient) from cytosol to capillaries
Asymmetric Cells (sidedness): protein targeting

65. Lipid Rafts Specific Microdomain
Glycosphingolipids
Cholesterol
GPI-linked proteins
Transmembrane signaling proteins
Caveolae — e.g. internalization of receptor-bound ligands

66. Lipid rafts Glycosphingolipids Cholesterol GPI-linked proteins
Transmembrane signaling proteins
Caveolae — e.g. internalization of receptor-bound ligands