Cholesterol effects on a mixed-chain phosphatidylcholine bilayer: a molecular dynamics simulation study

A molecular dynamics simulation of a mono-cis-unsaturated 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer containing ~22 mol% of cholesterol (POPC-Chol) was carried out for 15 ns. An 8-ns trajectory was analysed to determine the effects of Chol on the membrane properties and compare it with that on the fully saturated 1,2-dimyristoyl-phosphatidylcholine bilayer containing ~22 mol% of Chol (DMPC-Chol). The study suggests that the experimentally observed weaker effect of Chol on the POPC than DMPC bilayer might result from a different vertical localisation of the Chol hydroxyl group (OH-Chol) in both bilayers: in the POPC-Chol bilayer, OH-Chol is placed ~3 Å higher in the bilayer interface than in the DMPC-Chol bilayer. Because of the rigid cis double bond in the β-chain of POPC, Chol fits worse to the POPC-Chol membrane environment and is pushed up, in effect all Chol ring atoms are, on average, located above the double bond. Both in mono-cis-unsaturated and fully saturated PC bilayers, Chol induces stronger van der Waals interactions among the chains, whereas its interactions with the chains are weak. In contrast to DMPC, the smooth α-face of the Chol ring lowers the order of POPC chains, whereas the rough β-face increases the order.