Chapter 4Biomembranes: Their Structure, Che

mistry and Functions Learning objectives:

1. A brief history of studies on the structrure of the plasma membrane

2. Model of membrane structure: an experimental perspective

3. The chemical composition of membranes

4. Characteristics of biomembrane

5. 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. The history of study

Overton(1890s):

Lipid nature of PM;

To answer the question that how many lipid layers were in membrane, in 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 consisted of not one but two layers of lipids.

Gortter and Grendel(1925): The basis of membrane structure is a lipid bilayer

Cell 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 contain 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 differences, Davson and Danielli invoked the presence of proteins in membranes in 1935.

The plasma membrane is composed of a lipid bilayer that is lin

ed on both its inner and outer surface by a layer of globular prot

eins; in addition to , the presence of protein-lined pores for pola

r solutes and ions 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 Nicolson’s Model of membrane structure: The fluid-mosaic model is the “central dogma” of membrane biology.

A. The core lipid bilayer exists in a fluid state, capable of dynamic movement.

B. Membrane proteins form a mosaic of particles penetrating the lipid to varying degrees.

The Fluid Mosaic Model, 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 amphipathic.

There are three major 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 on membrane fluidity

The length of the fatty acid

The degree of unsaturation of their side chains

The temperature.

The effects of sterols on membrane fluidity

Liposome and application

Study on nature; gene transfer; as a carrier.

B. Membrane Proteins:

The “Mosaic” Part of the Model

Membranes contain integral, peripheral, and lipid-anchored proteins:

Rolled-up sheet

helixAmphipathic helix

lipid-anchored proteins

Noncovalent interactions

Integral proteins are amphipathic, with hydrophobic domains anchoring them in the bilayer and hydrophilic regions forming functional domains outside of the bilayer.

Channel 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.

Proteins can be seperated by SDS-polyacrylamide gel electrophoresis

The 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 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 CH3

Triton X-100:

Integral proteins are embedded in the membrane; their removal requires detergents.

C. Membrane Carbohydrates

Membrane 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 structures outside the cell.

Glycolipids have larger carbohydrate chains that may be cell-to-cell recognition sites.

4. Characteristics of biomembraneA. 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 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 membrane 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 HE

The asymmetry of membrane protein

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-fracture 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 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 adhesion

A. PM define the boundaries of the cell and organelles.

B. Compartmentalization: membranes form continuous sheets that enclose intracellular compartments.

C. Transporting solutes: membrane proteins facilitate the movement of substances between compartments.

D. Responding to external signals: membrane receptors transduce signals from outside the cell in response to specific ligands.

E. Intercellular interaction: membrane mediate recognition and interaction between adjacent cells by cell-to-cell communication and junction.

F. Locus for biochemical activities: membrane provide a scaffold that organizes enzymes for effective interaction.

G. Energy transduction: membranes transduce photosynthetic energy, convert chemical energy to ATP, and store energy in ion and solute gradients.

Analysis of membrane proteins by using of molecule biological technique