Interaction of cholesterol-like molecules in polyunsaturated phosphatidylcholine lipid bilayers as revealed by a self-consistent field theory

Cholesterol is one of the most abundant components in biological membranes. In this paper we apply a detailed state-of-the-art self-consistent field (SCF) theory to predict the influence of cholesterol-look-alikes in the bilayer composed of 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphatidylcholine (18:022:6omega3cis PC) lipids with a polyunsaturated 22:6 and a fully saturated 18:0 tail. The cholesterol-like molecule is composed of a hydroxyl group, a rigid chain fragment with length n segments and a branched semiflexible moiety with methylene side groups. We vary both the length of the rigid fragment in the cholesterol-look-alikes and their mole fraction in the tensionless bilayers. We find that these additives significantly increase the order of the saturated tails, but influence the conformational properties of the unsaturated tail much less. With increasing loading the bilayer thickness and the area available per PC head group increase. The hydroxyl group anchors close to the membrane-water interface, but with increasing loading the distribution of this polar group widens. The orientational order of the rigid part is high and we conclude that the cholesterol has significant mobility in the normal direction in the hydrophobic region of the bilayer indicating that one singly hydroxyl group is giving only a weak anchoring to the water-interface. Cholesterol-look-alikes increase the fluctuation of the tail ends and decrease the interdigitation of the tails. Several of our predictions correspond to molecular dynamics (MD) simulation results, but there are also important differences. Most notably the cholesterol-look-alikes can visit the membrane symmetry-plane more easily in SCF than in MD. Possible reasons for this are discussed.