细胞质膜与细胞表面

1、Chapter 4: Cell Membrane and Cell Surface,I. Cell Membrane II. Cell Junctions III. Cell Adhesion IV. Extracellular Matrix,I. Biomembranes: Their Structure, Chemistry and Functions,Learning objectives: A brief history of studies on the structrure of the plasma membrane Model of membrane structure: an

2、 experimental perspective The chemical composition of membranes Characteristics of biomembrane An overview of the functions of biomembranes,1. A brief history of studies on the structrure of the plasmic membrane,A. Conception: Plasma membrane(cell membrane), Intracellular membrane, Biomembrane. B. T

3、he history of study Overton(1890s): Lipid nature of PM;, J.D.Robertson(1959): The TEM showing:the trilaminar appearance of PM; Unit membrane model; S.J.Singer and G.Nicolson(1972): fluid-mosaic model; K.Simons et al(1997): lipid rafts model; Functional rafts in Cell membranes. Nature 387:569-572,2.

4、Singer and Nicolsons Model of membrane structure: The fluid-mosaic model is the “central dogma” of membrane biology.,The core lipid bilayer exists in a fluid state, capable of dynamic movement. Membrane proteins form a mosaic of particles penetrating the lipid to varying degrees.,The Fluid Mosaic Mo

5、del, proposed in 1972 by Singer and Nicolson, had two key features, both implied in its name.,3. The chemical composition of membranes,A. Membrane Lipids: The Fluid Part of the Model,Phospholipids: Phosphoglyceride and sphingolipids Glycolipids Sterols ( is only found in animals),Membrane lipids are

6、 amphipathic. There are three major classes of lipids:,Figure 10-2. The parts of a phospholipid molecule. Phosphatidylcholine, represented schematically (A), in formula (B), as a space-filling model (C), and as a symbol (D). The kink due to the cis-double bond is exaggerated in these drawings for em

7、phasis.,Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section. Lipid molecules form such structures spontaneously in water. The shape of the lipid molecule determines which of these structures is formed. Wedge-shaped lipid molecules (above) form micelles, whereas cylinder-shaped pho

8、spholipid molecules (below) form bilayers.,Figure 10-4. Liposomes. (A) An electron micrograph of unfixed, unstained phospholipid vesicles (liposomes) in water. The bilayer structure of the vesicles is readily apparent. (B) A drawing of a small spherical liposome seen in cross-section. Liposomes are

9、commonly used as model membranes in experimental studies. (A, courtesy of Jean Lepault.),Figure 10-5. A cross-sectional view of a synthetic lipid bilayer, called a black membrane. This planar bilayer is formed across a small hole in a partition separating two aqueous compartments. Black membranes ar

10、e used to measure the permeability properties of synthetic membranes.,Figure 10-6. Phospholipid mobility. The types of movement possible for phospholipid molecules in a lipid bilayer.,Figure 10-7. Influence of cis-double bonds in hydrocarbon chains. The double bonds make it more difficult to pack th

11、e chains together and therefore make the lipid bilayer more difficult to freeze.,Figure 10-8. The structure of cholesterol. Cholesterol is represented by a formula in (A), by a schematic drawing in (B), and as a space-filling model in (C).,Figure 10-9. Cholesterol in a lipid bilayer. Schematic drawi

12、ng of a cholesterol molecule interacting with two phospholipid molecules in one leaflet of a lipid bilayer.,Figure 10-10. Four major phospholipids in mammalian plasma membranes. Note that different head groups are represented by different symbols in this figure and the next. All of the lipid molecul

13、es shown are derived from glycerol except for sphingomyelin, which is derived from serine.,Figure 10-11. The asymmetrical distribution of phospholipids and glycolipids in the lipid bilayer of human red blood cells. The symbols used for the phospholipids are those introduced in Figure 10-10. In addit

14、ion, glycolipids are drawn with hexagonal polar head groups (blue). Cholesterol (not shown) is thought to be distributed about equally in both monolayers.,Figure 10-12. Glycolipid molecules. Galactocerebroside (A) is called a neutral glycolipid because the sugar that forms its head group is uncharge

15、d. A ganglioside (B) always contains one or more negatively charged sialic acid residues (also called N-acetylneuraminic acid, or NANA), whose structure is shown in (C). Whereas in bacteria and plants almost all glycolipids are derived from glycerol, as are most phospholipids, in animal cells they a

16、re almost always produced from sphingosine, an amino alcohol derived from serine, as is the case for the phospholipid sphingomyelin. Gal = galactose; Glc = glucose, GalNAc = N-acetylgalactos-amine; these three sugars are uncharged.,Figure 10-13. Six ways in which membrane proteins associate with the

17、 lipid bilayer. Most trans-membrane proteins are thought to extend across the bilayer as a single a helix (1) or as multiple a 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

18、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 atta

19、ched to the membrane only by noncovalent interactions with other membrane proteins (5) and (6). How the structure in (3) is formed is illustrated in Figure10-14.,Membrane proteins,Figure 10-14. The covalent attachment of either of two types of lipid groups can help localize a water-soluble protein t

20、o a membrane after its synthesis in the cytosol. (A) A fatty acid chain (either myristic or palmitic acid) is attached via an amide linkage to an amino-terminal glycine. (B) A prenyl group (either farnesyl or a longer geranylgeranyl group - both related to cholesterol) is attached via a thioether li

21、nkage to a cysteine residue that is four residues from the carboxyl terminus. Following this prenylation, the terminal three amino acids are cleaved off and the new carboxyl terminus is methylated before insertion into the membrane. The structures of two lipid anchors are shown underneath: (C) a myr

22、istyl anchor (a 14-carbon saturated fatty acid chain), and (D) a farnesyl anchor (a 15-carbon unsaturated hydrocarbon chain).,Figure 10-15. A segment of a transmembrane polypeptide chain crossing the lipid bilayer as an a helix. Only the a-carbon backbone of the polypeptide chain is shown, with the

23、hydrophobic amino acids in green and yellow. (J. Deisenhofer et al., Nature 318:618-624 and H. Michel et al., EMBO J. 5:1149-1158),Figure 10-17. A typical single-pass transmembrane protein. Note that the polypeptide chain traverses the lipid bilayer as a right-handed a helix and that the oligosaccha

24、ride chains and disulfide bonds are all on the noncytosolic surface of the membrane. Disulfide bonds do not form between the sulfhydryl groups in the cytoplasmic domain of the protein because the reducing environment in the cytosol maintains these groups in their reduced (-SH) form.,Figure 10-18. A

25、detergent micelle in water, shown in cross-section. Because they have both polar and nonpolar ends, detergent molecules are amphipathic.,Figure 10-19. Solubilizing membrane proteins with a mild detergent. The detergent disrupts the lipid bilayer and brings the proteins into solution as protein-lipid

26、-detergent complexes. The phospholipids in the membrane are also solubilized by the detergent.,Figure 10-20. The structures of two commonly used detergents. Sodium dodecyl sulfate (SDS) is an anionic detergent, and Triton X-100 is a nonionic detergent. The hydrophobic portion of each detergent is sh

27、own in green, and the hydrophilic portion is shown in blue. Note that the bracketed portion of Triton X-100 is repeated about eight times.,Figure 10-21. The use of mild detergents for solubilizing, purifying, and reconstituting functional membrane protein systems. In this example functional Na+-K+ A

28、TPase molecules are purified and incorporated into phospholipid vesicles. The Na+-K+ ATPase is an ion pump that is present in the plasma membrane of most animal cells; it uses the energy of ATP hydrolysis to pump Na+ out of the cell and K+ in, as discussed in Chapter 11.,Figure 10-22. A scanning ele

29、ctron micrograph of human red blood cells. The cells have a biconcave shape and lack nuclei. (Courtesy of Bernadette Chailley.),Figure 10-24. SDS polyacrylamide-gel electrophoresis pattern of the proteins in the human red blood cell membrane. The gel in (A) is stained with Coomassie blue. The positi

30、ons of some of the major proteins in the gel are indicated in the drawing in (B); glycophorin is shown in red to distinguish it from band 3. Other bands in the gel are omitted from the drawing. The large amount of carbohydrate in glycophorin molecules slows their migration so that they run almost as

31、 slowly as the much larger band 3 molecules. (A, courtesy of Ted Steck.),Figure 10-25. Spectrin molecules from human red blood cells. The protein is shown schematically in (A) and in electron micrographs in (B). Each spectrin heterodimer consists of two antiparallel, loosely intertwined, flexible po

32、lypeptide chains called a and b these are attached noncovalently to each other at multiple points, including both ends. The phosphorylated head end, where two dimers associate to form a tetramer, is on the left. Both the a and b chains are composed largely of repeating domains 106 amino acids long.

33、In (B) the spectrin molecules have been shadowed with platinum. (D.W. Speicher and V.T. Marchesi, Nature 311:177-180; B, D.M. Shotton et al., J. Mol. Biol. 131:303-329),Figure 10-26. The spectrin-based cytoskeleton on the cytoplasmic side of the human red blood cell membrane. The structure is shown

34、schematically in (A) and in an electron micrograph in (B). The arrangement shown in (A) has been deduced mainly from studies on the interactions of purified proteins in vitro. Spectrin dimers associate head-to-head to form tetramers that are linked together into a netlike meshwork by junctional comp

35、lexes composed of short actin filaments (containing 13 actin monomers), tropomyosin, which probably determines the length of the actin filaments, band 4.1, and adducin. The cytoskeleton is linked to the membrane by the indirect binding of spectrin tetramers to some band 3 proteins via ankyrin molecu

36、les, as well as by the binding of band 4.1 proteins to both band 3 and glycophorin (not shown). The electron micrograph in (B) shows the cytoskeleton on the cytoplasmic side of a red blood cell membrane after fixation and negative staining. (B, courtesy of T. Byers and D. Branton, PNSA. 82:6153-6157

37、),Figure 10-31. The three-dimensional structure of a bacteriorhodopsin molecule. The polypeptide chain crosses the lipid bilayer as seven a helices. The location of the chromophore and the probable pathway taken by protons during the light-activated pumping cycle are shown. When activated by a photo

38、n, the chromophore is thought to pass an H+ to the side chain of aspartic acid 85. Subsequently, three other H+ transfers are thought to complete the cyclefrom aspartic acid 85 to the extra-cellular space, from aspartic acid 96 to the chromophore, and from the cytosol to aspartic acid 96. (R. Hender

39、son et al. J. Mol. Biol.213:899-929),Figure 10-32. The three-dimensional structure of a porin trimer of Rhodobacter capsulatus determined by x-ray crystallography. (A) Each monomer consists of a 16-stranded antiparallel b barrel that forms a transmembrane water-filled channel. (B) The monomers tight

40、ly associate to form trimers, which have three separate channels for the diffusion of small solutes through the bacterial outer membrane. A long loop of polypeptide chain (shown in red), which connects two b strands, protrudes into the lumen of each channel, narrowing it to a cross-section of 0.6 x

41、1 nm. (Adapted from M.S. Weiss et al., FEBS Lett.280: 379-382),Figure 10-33. The three-dimensional structure of the photosynthetic reaction center of the bacterium Rhodopseudomonas viridis. The structure was determined by x-ray diffraction analysis of crystals of this transmembrane protein complex.

42、The complex consists of four subunits, L, M, H, and a cytochrome. The L and M subunits form the core of the reaction center, and each contains five a helices that span the lipid bilayer. The locations of the various electron carrier coenzymes are shown in black. (Adapted from a drawing by J. Richard

43、son based on data from J. Deisenhofer et al., Nature 318:618-624),4. Characteristics of biomembrane,A. Dynamic nature of biomembrane,Fluidity of membrane lipid. It give membranes the ability to fuse, form networks, and separate charge; Motility of membrane protein.,The lateral diffusion of membrane

44、lipids can demonstrated experimentally by a technique called Fluorescence Recovery After Photobleaching (FRAP).,Figure 10-34. Experiment demonstrating the mixing of plasma membrane proteins on mouse-human hybrid cells. The mouse and human proteins are initially confined to their own halves of the ne

45、wly formed heterocaryon plasma membrane, but they intermix with time. The two antibodies used to visualize the proteins can be distinguished in a fluorescence microscope because fluorescein is green whereas rhodamine is red. (Based on observations of L.D. Frye and M. Edidin, J. Cell Sci. 7:319-335),

46、Figure 10-35. Antibody-induced patching and capping of a cell-surface protein on a white blood cell. The bivalent antibodies cross-link the protein molecules to which they bind. This causes them to cluster into large patches, which are actively swept to the tail end of the cell to form a cap. The ce

47、ntrosome, which governs the head-tail polarity of the cell, is shown in orange.,Figure 10-37. Diagram of an epithelial cell showing how a plasma membrane protein is restricted to a particular domain of the membrane. Protein A (in the apical membrane) and protein B (in the basal and lateral membranes

48、) can diffuse laterally in their own domains but are prevented from entering the other domain, at least partly by the specialized cell junction called a tight junction. Lipid molecules in the outer (noncytoplasmic) monolayer of the plasma membrane are likewise unable to diffuse between the two domai

49、ns; lipids in the inner (cytoplasmic) monolayer, however, are able to do so.,Figure 10-38. Three domains in the plasma membrane of guinea pig sperm defined with monoclonal antibodies. A guinea pig sperm is shown schematically in (A), while each of the three pairs of micrographs shown in (B), (C), an

50、d (D) shows cell-surface immunofluorescence staining with a different monoclonal antibody (on the right) next to a phase-contrast micrograph (on the left) of the same cell. The antibody shown in (B) labels only the anterior head, that in (C) only the posterior head, whereas that in (D) labels only t

51、he tail. (Courtesy of Selena Carroll and Diana Myles.),Figure 10-39. Four ways in which the lateral mobility of specific plasma membrane proteins can be restricted. The proteins can self-assemble into large aggregates (such as bacteriorhodopsin in the purple membrane of Halobacterium) (A); they can

52、be tethered by interactions with assemblies of macromolecules outside (B) or inside (C) the cell; or they can interact with proteins on the surface of another cell (D).,Figure 10-41. Simplified diagram of the cell coat (glycocalyx). The cell coat is made up of the oligosaccharide side chains of glyc

53、olipids and integral membrane glycoproteins and the polysaccharide chains on integral membrane proteoglycans. In addition, adsorbed glycoproteins and adsorbed proteoglycans (not shown) contribute to the glycocalyx in many cells. Note that all of the carbohydrate is on the noncytoplasmic surface of t

54、he membrane.,cell coat,Figure 10-42. The protein-carbohydrate interaction that initiates the transient adhesion of neutrophils to endothelial cells at sites of inflammation. (A) The lectin domain of P-selectin binds to the specific oligosaccharide shown in (B), which is present on both cell-surface

55、glycoprotein and glycolipid molecules. The lectin domain of the selectins is homologous to lectin domains found on many other carbohydrate-binding proteins in animals; because the binding to their specific sugar ligand requires extracellular Ca2+, they are called C-type lectins. A three-dimensional

56、structure of one of these lectin domains, determined by x-ray crystallography, is shown in (C); its bound sugar is colored blue. Gal = galactose; GlcNAc = N-acetylglucosamine; Fuc = fucose; NANA = sialic acid.,5. An Overview of membrane functions,1. Define the boundaries of the cell and its organell

57、es. 2. Serve as loci for specific functions. 3. provide for and regulate transport processes. 4. contain the receptors needed to detect external signals. 5. provide mechanisms for cell-to-cell contact, communication and adhesion,Learning Objectives: 1. Integrating Cells into Tissues 2. Cell junctons

58、: Cell-cell adhension and communication; 3. Cell-Matrix adhension; 4. Extracellular matrix: Components and Functions; 5. Cell Walls,II. Cell junction, Cell adhension Extracellular matrix,Figure19-1Simplified drawing of a cross-section through part of the wall of the intestine.This long, tubelike org

59、an is constructed from epithelial tissues (red), connective tissues (green), and muscle tissues (yellow). Each tissue is an organized assembly of cells held together by cell-cell adhesions, extracellular matrix, or both.,Figure19-2The role of tight junctions in transcellular transport.Transport proteins are confined to different regions of the plasma membrane in epithelial cells of the small intestine. This segregation permits a vectorial transfer of nutrients across the epithelial sheet from the gut lumen to the blood. In the example shown, glucose is actively transported into t