Influence of Cholesterol on Phospholipid Bilayer Dynamics

Abstract

Surrounding every living cell is a membrane comprised of an assortment of lipids, cholesterol, and proteins. Bilayers are dynamic systems with phospholipid and cholesterol molecules diffusing within a leaflet and occasionally flipping between leaflets. In biological systems, bilayers can exist in two phases; liquid ordered or liquid disordered. Molecular dynamics (MD) simulations give windows of insight into the biophysical properties of these bilayers. In this study, the effects of cholesterol on lipid bilayers are investigated by examining a variety of phospholipid head groups, cholesterol concentrations, chain saturations, and chain lengths. Two fatty acid chains, dimyristoyl (DM) and dioleoyl (DO), were used in our initial simulations with a phosphatidylcholine head group. The DM chain was then studied with several other phospholipid head groups including phosphatidic acid, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylserine. In order to ensure that the MD simulations are physically accurate, the systems were checked at different simulation sizes as well as compared to earlier simulations, X-ray diffraction experiments, and NMR data. Simulations between 50 and 150ns at temperatures of either 303.15 or 333.15K elucidated the lipid ordering and phase behavior of these lipids in liquid disordered and liquid ordered phases. Increases in cholesterol concentration were seen to increase order in liquid disordered bilayers while simultaneously promoting disorder in bilayers which form gels in pure bilayers at temperatures of 303.15K.