Composition fluctuations, chemical exchange, and nuclear relaxation in membranes containing cholesterol

A thermodynamic model of cholesterol-phospholipid complexes is used as a starting point for calculating fluctuations in membranes containing cholesterol and phospholipids. The calculations describe fluctuations in the concentration of complexes formed between cholesterol and phospholipids with longer saturated fatty acid chains. The fluctuations in complex concentrations arise by two distinct mechanisms. In one, the chemical composition of the sample varies from point to point, and the concentration of the complexes varies according to local chemical equilibrium. In the second, the composition remains fixed, and the complexes form and dissociate according to chemical reaction kinetics. In both cases the nuclear resonance frequency of a deuterium labeled phospholipid undergoes fluctuations and line broadening as a consequence of the formation and dissociation of complexes. For a specific ternary lipid mixture at its critical composition, deuterium nuclear resonance line broadening of chain labeled phospholipids is calculated for temperatures up to 10°-20° above the miscibility critical temperature. This line broadening is associated with fluctuations in the degree of phospholipid chain ordering related to the formation and dissociation of complexes.