The stoichiometry and dynamics of lecithin-cholesterol clusters in bilayer membranes

Abstract

NMR experiments comparing the immobilisation of lecithin chains by cholesterol and by 5α-androstan-3β-ol confirm the 1 : 1 stoichiometry of the lecithinsterol complex and the molecular details of the interaction given by Darke et al. (Darke, A., Finer, E.G., Flook, A.G. and Phillips, M.C. (1972) J. Mol. Biol. 63, 265–279) (in particular, that the cholesterol OH lies next to the lecithin phosphate.) In bilayers containing less than equimolar amounts of cholesterol discrete regions of 1 : 1 complex separate out; this leaves (a) lecithin molecules at the boundaries of these regions, for which cooperative motions are not possible; and (b) clusters of free lecithin molecules in which the hydrocarbon chains undergo cooperative motions and which freeze at the usual gel-to-liquid-crystal transition temperature ( T c ). There is a significant fraction of the latter type of lecithin molecule only when less than about 30 mole % cholesterol is present. When the level of cholesterol in lecithin bilayers is decreased, the increase in free lecithin cluster size causes the motions of the hydrocarbon chains in these regions to become more cooperative such that the transition enthalpy per molecule of Type (b) approaches that of pure lecithin. At room temperature ( T > T c ), the exchange rate between complexed and uncomplexed lecithin probably lies between 10 −1s −1 and 10 2 s −1.