Role of lipids in the structure and function of biological membranes.

The concept of biological membranes as vesicular or tubular continua built up of nesting repeating units has been systematically explored and some of the relevant experimental work has been assembled. The bulk of the data have been drawn from studies on the mitochondrion, which is assumed to be a model for membranes generally. The repeating units of membranes are composite macromolecules containing both protein and lipid. The unit of the mitochondrial inner membrane is tripartite; the basepiece is the membrane-forming element. The four complexes of the electron transfer chain represent the different species of basepieces in the inner membrane. The repeating units of the outer mitochondrial membrane have a different form and size and a completely different set of enzymes (the enzymes of the citric and fatty acid oxidation cycles). The repeating units of the inner mitochondrial membrane are capable of forming membranes spontaneously. This membrane-forming capability is absolutely dependent on the presence of lipid. Evidence is presented for the view that lipid restricts the number of binding modalities and thus compels a two-dimensional alignment of repeating units. In absence of lipid three-dimensional stacking takes place, and the aggregates thus formed are, in effect, bulk phases. The membrane may be looked upon as a device for molecularizing repeating units, and it is this molecularization which underlies the essentiality of lipid for electron transfer. The theory of lipid requirement for enzymic activity is developed. The reconstitution of the electron transfer chain is shown to be essentially a membrane phenomenon rather than an expression of direct chemical interaction between the different parts of the electron transfer chain.