复旦大学细胞生物学课件04生物膜：结构、化学和功能

1、Chapter 4Biomembranes: Their Structure, Chemistry and Functions Learning objectives:A brief history of studies on the structrure of the plasma membrane Model of membrane structure: an experimental perspectiveThe chemical composition of membranesCharacteristics of biomembraneAn overview of the functi

2、ons of biomembranes A brief history of studies on the structrure of the plasmic membraneA. Conception: Plasma membrane(cell membrane), Intracellular membrane, Biomembrane.B. The history of studyOverton(1890s): Lipid nature of PM; To answer the question that how many lipid layers were in membrane, in

3、 1925 Gorter and Grendel extracted the lipids from a known number of erythrocytes and spread the lipid film on a water surface. The area of lipid film on the water was about twice(1.8-2.2) the estimated total surface area of the erythrocytes, so they concluded that the erythrocyte plasma membrane co

4、nsisted of not one but two layers of lipids. Gortter and Grendel(1925): The basis of membrane structure is a lipid bilayerCell physiologists(1920s and 1930s) : The decrease in surface tensions of PM might be explained by the proteins.H.Davson and J.Danielli(1935): “sandwich model” Membranes also con

5、tain proteins. If the membranes only consist of pure lipids, it could not explain all the properties of membranes. For example, sugars, ions, and other hydrophilic solutes move into and out of cells much more readily than could be explained by the permeability of pure lipid bilayers. To explain such

6、 differences, Davson and Danielli invoked the presence of proteins in membranes in 1935. The plasma membrane is composed of a lipid bilayer that is lined on both its inner and outer surface by a layer of globular proteins; in addition to , the presence of protein-lined pores for polar solutes and io

7、ns to enter and exit the cell. 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. Singer and Nicolsons Model

8、 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 Model, proposed in 1972 by Si

9、nger and Nicolson, had two key features, both implied in its name.3. The chemical composition of membranesA. Membrane Lipids: The Fluid Part of the Model Phospholipids: Phosphoglyceride and sphingolipids Glycolipids Sterols ( is only found in animals)Membrane lipids are amphipathic.There are three m

10、ajor classes of lipids:Three kinds of movement of Membrane lipids Three kinds of movement:Rotation about its long axis;Lateral diffusion by exchanging places;Transverse diffusion, or “flip-flop” from one monolayer to the other. Flippases catalyze the flip-flop.The effects of fatty acid composition o

11、n membrane fluidityThe length of the fatty acidThe degree of unsaturation of their side chainsThe temperature.The effects of sterols on membrane fluidityLiposome and application Study on nature; gene transfer; as a carrier.B. Membrane Proteins: The “Mosaic” Part of the ModelMembranes contain integra

12、l, peripheral, and lipid-anchored proteins:Rolled-up sheet helixAmphipathic helix lipid-anchored proteinsNoncovalent interactions Integral proteins are amphipathic, with hydrophobic domains anchoring them in the bilayer and hydrophilic regions forming functional domains outside of the bilayer. Chann

13、el proteins have hydrophilic cores that form aqueous channels in the membrane-spanning region. Peripheral proteins are attached to the membrane by weak bonds and are easily solubilizad. Lipid-attachored membrane proteins are distinguished by both the types of lipid anchor and their orientation.Prote

14、ins can be seperated by SDS-polyacrylamide gel electrophoresisThe orientation of integral proteins can be determined using nonpenetrating agents that label the proteins.Identification of transmembrane domains can be predicted from the amino acid sequence using a hydropathy plot.Membrane domains and

15、polarity.Protein/lipid ratios vary considerably among different membrane types.Lipid and protein components of membranes are bound together by non-covalent forces.Detergent- small amphipathic molecules SDS: CH3-(CH2)11-OSO3-Na+ CH3 CH3 CH3 C CH2 C (O-CH2-CH2)10- OH CH3 CH3Triton X-100:Integral prote

16、ins are embedded in the membrane; their removal requires detergents.C. Membrane CarbohydratesMembrane contain carbohydrates convalently linked to lipids and proteins on the extracellular surface of the bilayer.Glycoproteins have short , branched carbohydrates for interactions with other cells and st

17、ructures outside the cell.Glycolipids have larger carbohydrate chains that may be cell-to-cell recognition sites.4. Characteristics of biomembraneA. Dynamic nature of biomembraneFluidity of membrane lipid. It give membranes the ability to fuse, form networks, and separate charge;Motility of membrane

18、 protein.The lateral diffusion of membrane lipids can demonstrated experimentally by a technique called Fluorescence Recovery After Photobleaching (FRAP). B. The asymmetry of biomembranes The foundation of membrane function The asymmetry of membrane lipids and glycolipids : The inner and outer membr

19、ane leaflets were shown to have different lipid compositions. Lipld asymmentry gives the membrane leaflets different physical and chemical properties appropriate for the different interactions occurring at the two membrane faces.The asymmetric distribution of PL in HEThe asymmetry of membrane protei

20、n and glycoprotein :Integral proteins attach to the bilayer asymmetrically, giving the membrane a distinct “sidedness”.The membrane carbohydrates only distributing on ES face. Integral proteins have orientation within Membranes. The distribution of integral proteins can be analyzed by freeze-fractur

21、e and freeze-etching techniques.C. The inhomogeneity of membranes Lipid composition can influence the activity of membrane proteins and determine the physical state of the membrane.Biomembrane have agglomeration Model of Lipid raft in TGN 5. An Overview of membrane functions 1. Define the boundaries

22、 of the cell and its organelles. 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 adhesionPM define the boundaries of the cell and organelles.Compartmentalization: membranes form continuous