The effect of nonideal lateral mixing on the transmembrane lipid asymmetry.

It is shown that the equilibrium transmembrane lipid asymmetry strongly depends on the degree of nonideality in the lateral mixing of the lipid components. In two-component bilayers the effect of nonideal lateral mixing is maximal for a given component at mole fractions of this component between 0.35 and 0.4. For asymmetry creating factors about 3 kT correcting for lateral nonidealities typical for lipids can increase as much as three times the transmembrane asymmetry. The relationship between lateral nonideality and transbilayer asymmetry is analysed in detail in the case of electrostatically induced asymmetry by using the Gouy-Chapman theory of electric double layers and the Bragg-Williams (regular solutions) approximation of nonideal lateral mixing. Two representative models are studied: (a) a single flat bilayer with a transmembrane electric potential difference applied on it; (b) two parallel membranes at short separation. In case (a), for transmembrane potentials of about 50-100 mV the introduction of nonideality corrections increases up to 40% the transmembrane asymmetry. In case (b), at physiological electrolyte concentrations the lipid asymmetry and, consequently, the effect of lateral nonideality become significant only at unrealistically small separations between the membranes. The surprisingly great influence of the lateral nonideality on the equilibrium transmembrane asymmetry suggests a significant role for this effect in determining the membrane molecular organization. A restricted lateral lipid miscibility might serve as a peculiar, but rather strong 'amplifier' of the transmembrane asymmetry. The qualitatively different asymmetries found in small unilamellar phosphatidylcholine-phosphatidylethanolamine vesicles of different fatty acid composition (Lentz, B.R. and Litman, B.J. (1978) Biochemistry 17, 5537-5543) can be reasonably well explained as an effect of the lateral nonideality. A hypothesis considering the transmembrane distributions of the major phospholipid species in erythrocytes as evolving from their lateral miscibilities is proposed.