MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES

1. MOVEMENT OF MOLECULES ACROSS CELL MEMBRANES 物质的跨膜转运 XIA Qiang, MD & PhD Department of Physiology Room 518, Block C, Research Building School of Medicine, Zijingang Campus Email: xiaqiang@zju.edu.cn Tel: 88206417 (Undergraduate school), 88208252 (Medical school)

2. Outline Cell structure Simple diffusion Facilitated diffusion Active transport Endocytosis and exocytosis

3. Sizes, on a log scale

4. Electron Micrograph of organelles in a hepatocyte (liver cell)

5. Organelles have their own membranes

6. Cell Membrane (plasma membrane)细胞膜

7. Phospholipid bilayer

8. The amino acids along the membrane section are likely to have non-polar side chains Circles represent amino acids in the linear sequence of the protein Schematic cartoon of a transmembrane protein

9. Structure of cell membrane: Fluid Mosaic Model (Singer & Nicholson, 1972)

10. Drawing of the fluid-mosaic model of membranes, showing the phospholipid bilayer and imbedded proteins

11. Composition of cell membrane: • Lipids 脂类 • Proteins 蛋白质 • Carbohydrates 糖类

12. Lipid Bilayer Phospholipid Phosphatidylcholine Phosphatidylserine Phosphatidylethanolamine Phosphatidylinositol Cholesterol Sphingolipid

14. Rotation Lipid mobility reducing membrane fluidity enhancing membrane fluidity

15. Membrane proteins Integral (intrinsic) proteins Peripheral (extrinsic) proteins Integral protein Peripheral protein

16. Integral proteins

17. Adhesion Some glycoproteins attach to the cytoskeleton and extracellular matrix. Functions of membrane proteins

18. Carbohydrates Glycoprotein Glycolipid

19. Membrane Transport 跨膜转运 Lipid Bilayer -- primary barrier, selectively permeable

20. Membrane Transport • Simple Diffusion • Facilitated Diffusion • Active Transport • Endocytosis and Exocytosis Primary Active Transport Secondary Active Transport

21. Importance of pumps, transporters & channels • Basis of physiologic processes • Growth • Metabolic activities • Sensory perception • Basis of disease • Defective transporters (cystic fibrosis) • Defective channels (long QT syndrome, paralysis) • Basis of pharmacological therapies • Hypertension (diuretics) • Stomach ulcers (proton pump inhibitors)

22. START: Initially higher concentration of molecules randomly move toward lower concentration. Over time, solute molecules placed in a solvent will evenly distribute themselves. Diffusional equilibrium is the result (Part b).

23. At time B, some glucose has crossed into side 2 as some cross into side 1.

24. Note: the partition between the two compartments is a membrane that allows this solute to move through it. Net flux accounts for solute movements in both directions.

25. Simple Diffusion 单纯扩散 • Relative to the concentration gradient • movement is DOWN the concentration gradient ONLY (higher concentration to lower concentration) • Rate of diffusion depends on • The concentration gradient • Charge on the molecule • Size • Lipid solubility • Temperature

26. Simple diffusion & gap junctions

27. Facilitated Diffusion 易化扩散 • Carrier-mediated diffusion 载体中介的扩散 • Channel-mediated diffusion 通道中介的扩散

28. A cartoon model of carrier-mediated diffusion The solute acts as a ligand that binds to the transporter protein…. … and then a subsequent shape change in the protein releases the solute on the other side of the membrane.

29. In simple diffusion, flux rate is limited only by the concentration gradient. In carrier- mediated transport, the number of available carriers places an upper limit on the flux rate.

30. Characteristics of carrier-mediated diffusion: net movement always depends on the concentration gradient • Specificity • Saturation • Competition

31. Channel-mediated diffusion 3 cartoon models of integral membrane proteins that function as ion channels; the regulated opening and closing of these channels is the basis of how neurons function.

32. A thin shell of positive (outside) and negative (inside) charge provides the electrical gradient that drives ion movement across the membranes of excitable cells.

33. The opening and closing of ion channels results from conformational changes in integral proteins. Discovering the factors that cause these changes is key to understanding excitable cells.

34. Characteristics of ion channels • Specificity • Gating

35. Three types of passive, non-coupled transport through integral membrane proteins

38. I II III IV Outside + + + + + + + + + + + + Inside NH2 CO2H Voltage-gated Channel • e.g. Voltage-dependent Na+ channel

39. Na+ channel

40. Na+ channel Balloonfish or fugu

41. Closed Activated Inactivated Na+ channel conformation • Open-state • Closed-state

42. Ligand-gated Channel • e.g. N2-ACh receptor channel

43. Stretch Closed Open Stretch-sensitive Channel

44. Aquaporin • Aquaporins are water channels that exclude ions • Aquaporins are found in essentially all organisms, and have major biological and medical importance

45. The Nobel Prize in Chemistry 2003 "for discoveries concerning channels in cell membranes" "for structural and mechanistic studies of ion channels" "for the discovery of water channels" Peter Agre Roderick MacKinnon http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2003/popular.html

46. The dividing wall between the cell and the outside world – including other cells – is far from being an impervious shell. On the contrary, it is perforated by various channels. Many of these are specially adapted to one specific ion or molecule and do not permit any other type to pass. Here to the left we see a water channel and to the right an ion channel.

47. Peter Agre’s experiment with cells containing or lacking aquaporin. The aquaporin is necessary for making the cell absorb water and swell

48. Passage of water molecules through the aquaporin AQP1. Because of the positive charge at the center of the channel, positively charged ions such as H3O+, are deflected. This prevents proton leakage through the channel.

49. Model for water permeation through aquaporin

50. membrane In both simple and facilitated diffusion, solutes move in the direction predicted by the concentration gradient. In active transport, solutes move opposite to the direction predicted by the concentration gradient.