医学细胞生物学：第二篇 细胞的结构与功能

1、Location, structure,Molecular components,Function,A,B,细胞的生命活动及生命现象： 简单说包括生、老、病、死 具体说包括细胞的分化、生长与分裂、细胞的运动、遗传与变异、细胞的 物质与能量代谢、细胞对外界刺激的应答、细胞的衰老与死亡。,细胞的结构与功能,第二篇 细胞的结构与功能,细胞膜与物质的跨膜运输,细胞内膜系统与囊泡转运,线粒体与细胞能量转换,细胞核,细胞骨架与细胞的运动,细胞与细胞粘连,细胞外基质及功能,第四章 细胞膜与物质的跨膜运输,细胞膜的化学组成与分子特点； 小分子物质的跨膜运输; 大分子与颗粒物质的跨膜运输； 细胞表面及特化结构；

2、 细胞膜异常与疾病,细胞膜,第一节 细胞膜的化学组成与分子结构,一. 细胞膜的化学组成,（一）膜脂构成细胞膜的基本骨架,膜脂（membrane lipid）,磷脂,胆固醇,糖脂,第一节 细胞膜的化学组成与分子结构,一. 细胞膜的化学组成,（一）膜脂构成细胞膜的基本骨架,膜脂（membrane lipid）,磷脂,胆固醇,糖脂,Figure 10-3 Molecular Biology of the Cell ( Garland Science 2008),PE,PS,PC,Figure 10-3 Molecular Biology of the Cell ( Garland Science 2

3、008),PE,PS,PC,Figure 10-3 Molecular Biology of the Cell ( Garland Science 2008),PE,PS,PC,Figure 10-3 Molecular Biology of the Cell ( Garland Science 2008),PE,PS,PC,Figure 10-18 Molecular Biology of the Cell ( Garland Science 2008),Figure 10-4 Molecular Biology of the Cell ( Garland Science 2008),膜脂,

4、磷脂：膜脂的基本成分，50%,胆固醇：稳定膜和调节膜的流动性,糖脂：5% 以下，位于细胞的膜外,Figure 10-5 Molecular Biology of the Cell ( Garland Science 2008),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 t

5、hese structures is formed. Wedge-shaped lipid molecules (above) form micelles, whereas cylinder-shaped phospholipid molecules (below) form bilayers.,Figure 10-11 Molecular Biology of the Cell ( Garland Science 2008),Figure 10-12 Molecular Biology of the Cell ( Garland Science 2008),The importance of

6、 the lipid bilayer,The lipids of a membrane are more than simple structural elements: It is a skeleton of the membrane Lipid composition can determine the physical state of the membrane and influence the activity of particular membrane proteins. Membrane lipids also provide the precursors for highly

7、 active chemical messengers that regulate cellular function.,Figure 10-1c Molecular Biology of the Cell ( Garland Science 2008),（二）膜蛋白执行细胞膜的多种重要的功能,膜蛋白,内在膜蛋白（intrinsic membrane protein）,整合膜蛋白（integral membrane protein）,外在膜蛋白(extrinsic membrane protein),脂锚定蛋白（lipid anchored protein),外周蛋白（peripheral p

8、rotein）,脂连接蛋白（lipid-linked protein）,（三）膜糖类覆盖了细胞膜表明,二. 细胞膜的特性,1. 膜脂的不对称性,2. 膜蛋白的不对称性,3. 膜糖的不对称性,（一）不对称性,（二）膜的流动性是膜功能活动的保证,fluidity,1. 膜脂双分子层是二维流体,液晶态（liquid-crystal state),2. 膜脂分子能进行多种运动,3. 多种因素影响膜脂的流动性,（1）脂肪酸链的饱和程度,（2）脂肪酸链的长短,（3）胆固醇的双重调节作用,（4）卵磷脂与鞘磷脂的比例,（5）膜蛋白的影响,相变温度上，减慢运动,相变温度下，促进运动,相变温度的概念,4. 膜蛋白

9、的运动性,（1）侧向运动,（2）旋转运动,三. 细胞膜的分子结构模型,最初发现膜双层磷脂结构的是E. Gorter 和Grendel 从血影中 提取脂质。,（一）片层结构模型,To 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.,（二）单位膜模型,20世纪50s J.D Robertso

10、n,（三）流动镶嵌模型 fluid-mosaic model,In 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 molecule

11、s enter and leave 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 degree,模型强调了膜的流动性及不对称性,1975年 D.F Wallach 提出了一种“晶格镶嵌模型” （crystal mosaic mode

12、l),1977年M.KJain 和H.B White 又提出了“板块镶嵌模型”（block mosaic model）,（四）脂筏模型（严格说，它不是模型而是一种特殊的结构）,第二节 小分子物质的跨膜运输,一. 膜的选择性通透和简单扩散,二.膜转运蛋白介导的跨膜运输,膜转运蛋白（membrane transport protein）,Carrier Protein,Channel Protein,（一）离子通道转移各种离子,Ion channel,Passive transport,Specificity for the ion size and charge,High speed of tr

13、ansporting , 106 to 108 /second,Conformation changes from opening to closing,K+漏通道, 是持续开放的，大多数离子通道是受闸门控制的,Figure 11-31 Molecular Biology of the Cell ( Garland Science 2008),（二）载体蛋白介导的易化扩散,Facilitated diffusion,（三）载体蛋白介导的主动运输,1.离子泵直接水解ATP进行主动运输,钙泵,2. 离子驱动的协同运输,Cotransport: coupled transport A special

14、 kind of active transport,Two 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 propel the dri

15、ver.,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.,Antiport The driver and passenger travel in opposite directions.,Na+-H+ exchange carrier,Cl-HCO3- exchanger

16、,The energy of ATP may be used directly or indirectly. Direct Active Transport. Some transporters bind ATP directly and use the energy of its hydrolysis to drive active transport. Indirect Active Transport. Other transporters use the energy already stored in the gradient of a directly-pumped ion. Di

17、rect active transport of the ion establishes a concentration gradient. When this is relieved by facilitated diffusion, the energy released can be harnessed to the pumping of some other ion or molecule.,第三节 大分子和颗粒物质 的跨膜运输,Endocytosis,Exocytosis,一. 胞吞作用,（一） 吞噬作用,phagocytosis,A. Phagocytosis,Cell eatin

18、g: cells engulf particles with pseudopodia and pinches off a food vacuole. Two examples: 1.White Blood Cell 2.Amoeba,White Blood Cell,Bacteria,Phagocytosis: The uptake of large particles,Including: macromolecules, cell debris, even microorganisms and other cells. Phagocytosis is usually restricted t

19、o specialized cells called Phagocytes. Phagocytosis is initiated by cellular contact with an appropriate target. Phagocytosis may be stimulated by the opsonins Phagocytosis is driven by contractile activities of MF.,（二）胞饮作用,Pinocytosis,B. Pinocytosis,Cell drinking: droplets of extracellular fluid ar

20、e absorbed into the cell by small vesicles. Example:,（三）受体介导的内吞作用,C. Receptor-Mediated Endocytosis,Importing specific macromolecules (hormones) into the cell by the inward budding of vesicles formed from coated pits (receptors).,In most animal cells, clathrin-coated pits and vesicles provide an effi

21、cient pathway for taking up specific macromolecules from the extracellular fluid. In this process the macromolecules bind to complementary transmembrane receptor proteins, accumulate in coated pits, and then enter the cell as receptor-macromolecule complexes in clathrin-coated vesicles.,Receptor-med

22、iated endocytosis provides a selective concentrating mechanism that increases the efficiency of internalization of particular ligands more than a hundredfold, so that even minor components of the extracellular fluid can be specifically taken up in large amounts without taking in a correspondingly large volume of extracellular fluid.,clathrin,二. 胞吐作用,（一）结构性分泌途径（constitutive secretion pathway),（二）条件性分泌途径（regulated secretion pathway),第四节 细胞表面及其特化结构,一. 细胞外被和胞质溶胶,Cell coat or glycocalyx,二.细胞表面的特化结构,1.微绒毛,2. 纤毛与鞭毛