THE INFLUENCE OF CHOLESTEROL ON NEAREST-NEIGHBOR RECOGNITION IN SATURATED PHOSPHOLIPID-MEMBRANES

The thermodynamic preference for one phospholipid to become a covalent ly attached nearest neighbor of another in the bilayer state provides unique insight into the supramolecular structure of that membrane [Kri sovitch, S.M.;Regen, S.L.J. Am. Chem. Soc. 1992, 114, 9828]. In this w ork, such ''nearest-neighbor recognition'' measurements have been used to study the effects of cholesterol on phospholipid mixing in the phy siologically relevant fluid phase and in the gel-fluid coexistence reg ion. Specific disulfide-based dimers that have been employed were deri ved from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmi toyl-sn-glycero-3-phosphoethanolamine, and 1,2-distearoyl-sn-glycero-3 -phosphoethanolamine. When the difference in alkyl chain length betwee n the equilibrating monomers is small (i.e., two methylene groups per chain), the presence of cholesterol (10, 30, and 40 mol%) has no effec t on the dimer distribution; in each case, a statistical mixture is ob served. This finding establishes that these monomeric units are random ly arranged in the bilayer at the molecular as well as the supramolecu lar level. When the difference in chain length is increased to four me thylene units, high concentrations of cholesterol (greater-than-or-equ al-to 30 mol %) significantly enhance homodimer formation in the fluid phase but not in the gel-fluid region. It has also been found that in creasing concentrations of cholesterol result in increased rates of di mer equilibration in the fluid and gel-fluid states. The biological im plications of these nearest-neighbor recognition studies are briefly d iscussed.