医学细胞生物学：细胞膜结构与跨膜运输

1、Cell membrane and transmembrane transportation Cell membraneThe major points of cell membraneChemical components of membraneStructure of membraneModel of membrane Across membrane transport of small moleculesAcross membrane transport of large moleculesand particlesCell surface and its specified struc

2、tureAbnormality of cell membrane and diseases What are the functions of cytoplasm membrane ?An overview of membrane functions It hosts proteins for substance transport and signaling transductionIt is the boundary of a cell.It has the selective means for transporting substances.It has the machineries

3、 for the cell to communicate with outside signaling or stimuli.Chemical components of cell membrane ?Lipids constitute the skeleton of the membranemembrane lipidsphospholipidscholesterolglycolipidMembrane proteinsintrinsic membrane protein（integral membrane protein）extrinsic membrane protein（periphe

4、ral protein）lipid anchored protein(lipid-linked protein)Membrane protein takes specific role for the membraneWhy should we call the membrane lipids amphiphilic structure? phospholipidsFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell (

5、Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-18 Molecular Biology of the Cell ( Garland Sci

6、ence 2008)GlycolipidsFigure 10-4 Molecular Biology of the Cell ( Garland Science 2008)Cholesterol What are the ratios and functions of the 3 membrane lipids?Membrane lipidphospholipids：basic components，50%Cholesterol :stabilize membrane structure and modulate the fluidity of membraneglycolipid：5% or

7、 less，located outer layer of membraneHow to judge a membrane protein to be a intrinsic or extrinsic proteins? GPI linked lipidWhy should the Phospholipids spontaneously form bilayers?The pioneer researchers on cell membrane were E. Gorter and GrendelBlood ghost: red blood cell membrane(Hypotonic sol

8、ution or water.)Sandwish modelTo account for permeability of membrane to non-lipid substances, Danielli and Davson proposed sandwich model (later proved wrong) with phospholipid bilayer between layers of protein. Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section. Lipid molecules

9、 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 phospholipid molecules (below) form bilayers.liposomeFigure 10-12 Molecular Biology of the Cell (

10、Garland Science 2008)How do you describe the status of bilayer lipids of the membrane?The lipid bilayers is a two-dimensional fluidLiquid crystal stateWhat are the factors impact the fluidity of membrane lipids?Many factors impacting the fluidity of the lipids（1）the saturation of the fatty chain（2）t

11、he length of the fatty chain（3）cholesterol （4）the ratio of phosphotidal choline(PC) and sphingomylin(SM) （5）membrane proteinsPhase transition temeperature: a point at which lower than it will be solid and higher than it will be liquid.T phase-transition temperature, reducing fluidityT phase-transiti

12、on temperatureIncreasing fluidityHow many kinds of movements of membrane lipids?How many kinds of movements of membrane proteins?What experiments did people used to detect the movement of membrane proteins?1）lateral diffusion Fluorenscence recovery after photobleaching Fluorenscence loss in photoble

13、aching2）rotationWhat are the most important characteristics of cell membrane? The fluidity and asymmetryFluidity : both proteins and lipids are in motionAsymmetry 1. Asymmetry of lipids2. Asymmetry of proteins3. Asymmetry of sugar-chainsHow many models were raised to describe the nature structure of

14、 cell membrane?Why fluid-mosaic model is popularly accepted?Sandwish modelTo account for permeability of membrane to non-lipid substances, Danielli and Davson proposed sandwich model (later proved wrong) with phospholipid bilayer between layers of protein. unit membrane model20C.C 50s J.D RobertsonF

15、luid-mosaic modelIn 1972, Singer and Nicolson introduced the currently accepted fluid-mosaic model of membrane structure. In this model, a flexible layer made of lipid molecules is interspersed with large protein molecules that act as channels, transporters through which other molecules enter and le

16、ave the cell. There are also receptors in the membrane. 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 degreeThe model described the fluidity and asymmetry of the membrane1975年 D.F Wallach 提出了一

17、种“晶格镶嵌模型” （crystal mosaic model)1977年M.KJain 和H.B White 又提出了“板块镶嵌模型”（block mosaic model）What is lipid raft ？ What are the specific roles of lipid raft?lipid raft（严格说，它不是模型而是一种特殊的结构）Special components in lipid rafts1. Outer layer of lipids contains more sphingomyelin cholesterol , GPI anchored protei

18、n, long and saturated Fatty chains, less fluidity.2. A lot of transmembrane proteins.3. Inner layer with some anchored protein ,enzymes. 4. provide a platform for some protein conformation changes.How many ways are there in the small molecule cross membrane transportation?人工制作的脂质体和细胞膜在运输小分子物质方面有何异同？

19、What is called facilitated diffusion?Carrier protein mediated facilitated diffusionWhats the function of ion channels? ion channels transporting various ionsIon channel Passive transport Specificity for the ion size and chargeHigh speed of transporting , 106 to 108 /secondConformation changes from o

20、pening to closingK+ channel constitutively opens，while most channels are gated openingAquaporin, AQP How many kinds of ion pump in different cells? And their biological functions?ATP pumpP-class ion pumpV-class proton pumpF-class proton pumpABC transportWhat is multi-drug resistance (MDR) transport

21、protein?Ion pump hydrolyze ATP for active transportP-pumpP-pumpF-pumpMDR1(multidrug-resistance transport protein)Using ATP to transport drug out of the cellsColchicine , vinblastine (chemotherapy )ABC transport钙泵(Ca2+ pump)What is co-transport? ion-driven cotransportersCotransport: coupled transport

22、 A special kind of active transportTwo molecules travel together, one as a passenger, the other as a driver. The driver diffuses down its electrochemical gradient, but it cannot do so unless it has the passenger. ATP is not directly involved, but it sets up the electrochemical gradient used to prope

23、l the driver.Symport The passenger and the driver are transported in the same direction. Na-glucose symport takes place in the intestine, from the gut lumen to the insides of the cells lining the gut.AntiportThe driver and passenger travel in opposite directions.Na+-H+ exchange carrierCl-HCO3- excha

24、ngerHow to keep yourself slim ?Why do you think that the processes of intestine intakes glucose and stomach generate HCl belong to active transporting?What are endocytosis and exocytosis?Transport of Macromolecules or particlesEndocytosisExocytosisBacteriaPhagocytosisCell eating: cells engulf partic

25、les with pseudopodia and pinches off a food vacuole.Two examples:1.White Blood Cell2.AmoebaWhite Blood CellBacteriaPinocytosisCell drinking: droplets of extracellular fluid are absorbed into the cell by small vesicles.Example:Food ParticlesWhat is receptor-mediated endocytosis ?Receptor-Mediated End

26、ocytosisImporting specific macromolecules (hormones) into the cell by the inward budding of vesicles formed from coated pits (receptors). HormonesReceptorsLiver CellclathrinWhat is called cell coat or glycocalyx?Cell coat or glycocalyx (细胞外被和胞质溶胶)What are the functions of sugar chain of the cell mem

27、brane?What is the mechanism of cystinuria(胱氨酸尿症)？ Membrane abnormality and diseasesThe abnormality of carrier protein and diseasescystinuria(胱氨酸尿症)Membrane transporter disease ,genetic diseaseThe carriers in the absorbing epithelia of kidney tubulesfor transporting cystine and bi-NH2 amino acids( Ly

28、s, Arg,and ornithine) go wrong, or functionally defective, result in a disease.pH5-7 ，the saturation concentration of cystine is 0.3-0.4g/L Kidney stonerenal glycosuria (肾性糖尿)Abnormality of ion channels and diseases Abnormality of membrane receptor and diseasesfamilial hypercholesteroleminamyasthenia gravis(重症肌无力)Autoimmonity disease， anti-N-Ach receptor antibodies exist in bodymyasthenia gravis(重症肌无力)Autoimmonity disease， anti-N-Ach receptor