Membrane components

The main components of membranes are lipids and proteins although it is usual to find some carbohydrate as well. Lipids usually constitute about 25–50% of the dry weight of plasma membranes and consist mainly of phospholipids, glycolipids and cholesterol. The nature of the fatty acids does not seem to be fixed and may vary according to the temperature and other conditions. It appears to be essential that the fluidity of the membrane is maintained.

The lipid character of membranes explains their high electrical resistance, their ready destruction by lipolytic agents, and why they are permeable to lipid-soluble materials but have a low permeability for ions and most polar molecules. The presence of protein accounts for their mechanical strength, low surface tension and high specific conductance. The membrane proteins are also responsible for the specific properties of membranes and different types of protein are found in different membranes.

In aqueous solutions most phospholipids and glycolipids will assemble themselves into double layers in which the polar ends of the molecules are directed outwards and the long fatty acid chains are directed inwards as befits their amphiphilic nature (Figure 8.2b). Bimolecular lipid structures of this type are an essential feature of membrane structure.

Membranes also contain relatively large amounts of cholesterol which is thought to increase the mechanical stability and to help regulate the fluidity of the membrane. The relatively flat steroid ring is inserted between the phospholipid molecules with the polar −OH group adjacent to the polar heads of the phospholipids (Figure 15.2).

The most widely applicable model of membrane structure which allows for the physicochemical properties of membrane lipids and proteins and accounts for the dynamic nature and versatility of membranes is the fluid mosaic model (Figure 15.3). According to this the membrane is composed of a two-dimensional array of phospholipid and globular protein molecules in which the protein molecules are floating in a phospholipid continuum. About 70–80% of the protein molecules are integral proteins, which are held in association with the lipid bilayer by hydrophobic interactions. They, like the lipids, are amphiphilic and form an essential part of the structure. Other proteins known as peripheral or surface proteins can be dissociated from the membrane by the addition of salts. From this it is concluded that they are bound to the membrane surface by hydrogen bonds and salt linkages.

The functions of membrane proteins are many, varied and specific; they include transport, communication and energy transductions. Membranes are asymmetrical and the properties of their two surfaces are different.

All eukaryotic cells have carbohydrate groupings on their external surface. These are mainly the oligosaccharide side chains of glycoproteins and glycolipids. In addition the ‘cell coat’ may contain secreted glycoproteins and proteoglycans (page 407). The cell surface carbohydrates contain mannose, fucose and sialic acid in addition to glucose, glucosamine, galactose and galactosamine. The sialic acid is usually found at the ends of the side chains which are often branched, and it is the sialic acid which is believed to be mainly responsible for the negative charge found on the surface of all eukaryotic cells. The cell surface carbohydrates play an important role in recognition processes and cellular interactions.

The structure of membrane proteins

Structural studies on integral proteins suggest that the portions of polypeptide chain which are located within the lipid bilayer take up an α-helical conformation. Thus the membrane-crossing regions of these proteins have a relatively rigid rod-like structure. Two structurally distinct classes of integral protein occur. In the first class, which could be described as anchored proteins, the active site of the protein is held in the aqueous environment at the membrane surface while a single helical segment of protein traverses the membrane anchoring the protein within it (Figure 15.4a). Examples of this type of protein are the intestinal hydrolases as well as hormone receptors and antigens such as the histocompatibility antigens on which recognition sites are presented at the membrane surface. The integral proteins which function in membrane transport and as ‘gates’ have a different type of structure. The part within the membrane which forms the transporting region is complex and is made up of a cluster of transmembrane helices (Figure 15.4b). The sodium pump and the calcium pump of muscle are proteins of this type.

Membrane transport and membrane gates

Biological membranes are selectively permeable. They allow free diffusion of certain materials but act as a barrier towards others. In addition, they possess special pumping or active transport mechanisms which are responsible for the uptake or elimination of particular substances and which ensure that the composition of the enclosed compartment is closely controlled.

The physical forces responsible for the movement of materials across membranes, although based on diffusion and osmosis and the existence of electrochemical gradients, are extremely complex since they are affected not only by the composition of the membrane but also by such factors as the molecular size, lipid solubility, charge and degree of hydration of the penetrant as well as on its relative concentrations on the two sides of the membrane. Furthermore, many different substances are moving at the same time and the movement of one may have an effect on the movement of others.

The distribution of ions on the two sides of a membrane is also affected by the presence of large charged non-diffusible molecules, e.g. proteins and nucleic acids, which may themselves be unequally distributed.

Without considering in detail the factors mentioned above, it may be stated that most membranes will allow the passage of small uncharged molecules by simple diffusion and that the rate of their passage is related to their lipid solubility. The passage of other materials may occur as a result of the presence of pores, polar regions and gates over a small area of the membrane surface. Certain evidence suggests that the average pore is about 0·3–0·4 nm in diameter. A molecule that is larger than this will not cross the membrane passively, and for reasons given above neither will some smaller molecules.