Structure of the cell membrane

All living cells are surrounded by a plasma membrane composed of lipids and proteins, whose main function is to control the passage of substances into and out of the cell. In general, the role of the lipids is to furnish a continuous matrix that is impermeable even to the smallest ions, in which proteins are embedded to provide selective pathways for the transport of ions and organic molecules both down and against the prevailing gradients of chemical activity. The ease with which a molecule can cross a cell membrane depends to some extent on its size, but more importantly on its charge and lipid solubility. Hence the lipid matrix can exclude completely all large water-soluble molecules and also small charged molecules and ions, but is permeable to water and small uncharged molecules like urea. The nature of the transport pathways is dependent on the specific function of the cell under consideration. In the case of nerve and muscle, the pathways that are functionally important in connection with the conduction mechanism are (1) the voltage-sensitive sodium and potassium channels peculiar to electrically excitable membranes, (2) the ligand-gated channels at synapses that transfer excitation onwards from the nerve terminal, and (3) the ubiquitous sodium pump which is responsible in all types of cell for the extrusion of sodium ions from the interior.

The essential feature of membrane lipids that enables them to provide a structure with electrically insulating properties, i.e. to act as a barrier to the free passage of ions, is their possession of hydrophilic (polar) head groups and hydrophobic (non-polar) tails. When lipids are spread on the surface of water, they form a stable monolayer in which the polar ends are in contact with the

Fig. 3.1. Schematic diagram of the structure of a cell membrane. Two layers of phospholipid molecules face one another with their fatty acid chains forming a continuous hydrocarbon layer (HC) and their polar head groups (Pol) in the aqueous phase. The selective pathways for ion transport are provided by proteins extending across the membrane, which have a central hydrophobic section with non-polar side chains (NP), and hydrophilic portions projecting on either side.

Fig. 3.1. Schematic diagram of the structure of a cell membrane. Two layers of phospholipid molecules face one another with their fatty acid chains forming a continuous hydrocarbon layer (HC) and their polar head groups (Pol) in the aqueous phase. The selective pathways for ion transport are provided by proteins extending across the membrane, which have a central hydrophobic section with non-polar side chains (NP), and hydrophilic portions projecting on either side.

water and the non-polar hydrocarbon chains are oriented more or less at right angles to the plane of the surface. The cell membrane consists basically of two lipid monolayers arranged back-to-back with the polar head groups facing outwards, so that the resulting sandwich interposes between the aqueous phases on either side an uninterrupted hydrocarbon phase whose thickness is roughly twice the hydrocarbon chain length (Fig. 3.1). Lipid bilayersof this type can readily be prepared artificially, and such so-called 'black membranes' have provided a valuable model for the study of some of the properties of real cell membranes. The chemical structure of the phospholipids of which cell membranes are mainly composed is shown in Fig. 3.2. They have a glycerol backbone esterified to two fatty acids and phosphoric acid, forming a phosphatidic acid with which alcohols like choline or ethanolamine are combined through another ester linkage to give the neutral phospholipids lecithin and cephalin, or an amino acid like serine is linked to give negatively charged phos-phatidylserine. Another constituent of cell membranes is cholesterol, whose physical properties are similar to those of a lipid because of the —OH group attached to C-3. Spin-label and deuterium nuclear magnetic resonance studies of lipid bilayers have shown that the hydrocarbon chains are packed rather loosely so that the interior of the bilayer behaves like a liquid. With a chain length of 18 carbon atoms, the effective thickness of the hydrophobic region

Structure of the cell membrane 27

Cholesterol ch2-0-c0-r I

0"

Phosphatidylcholine (lecithin)

0"

Phosphatidylethanolamine (cephalin)

Fig. 3.2. The chemical structure of cholesterol and two neutral phospholipids.

is about 3.0 nm, which is consistent with the observed electrical capacitance of 1 ^F/cm2 membrane and a dielectric constant of 3.

Thanks to the advent of cDNA sequencing studies (see p. 59), our understanding of the organization of the protein moiety of the membrane has made rapid advances in recent years. Sections stained with permanganate or osmic acid for high resolution electron microscopy (Fig. 3.3) show the membrane in all types of cell to appear as two uniform lines separated by a space, the width of the whole structure being about 7.5 nm. This fits with the model proposed by Davson and Danielli, according to which the lipid bilayer is stabilized by a thin coating of protein molecules on either side, and the electron-dense stain is taken up by the polar groups of the phospholipids and of the

Fig. 3.3. Electron micrograph at high magnification of the cell membrane stained with osmic acid. Reproduced by courtesy of Professor J. D. Robertson.

proteins associated with them. However, an examination of freeze-fractured membranes under the electron microscope (Fig. 3.4) indicates that those proteins which traverse the bilayer to form specific ion-conducting or ion-pumping pathways are sometimes visible as globular indentations or projections. Such membrane proteins have a central non-polar section that is at home in the hydrophobic environment provided by the hydrocarbon chains of the lipids, together with polar and often glycosidic portions extending into the aqueous medium both inside and outside. Whether they are held in a fixed position in the membrane by internal fibrils, or are free to rotate and move laterally, is not always clear, but it may well be that some freedom of movement is necessary for their normal functioning.

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