Investigating the effects of cholesterol on phospholipid bilayer with molecular dynamics simulations

Abstract

This PhD project studies the effects of cholesterol in phospholipid bilayer using molecular dynamics (MD) simulations. Dipalmitoylphosphatidylcholine(DPPC) bilayers with cholesterol concentrations between 0% and 40% were simulated using all-­‐atom CHARMM36 force filed. The main concerned aspects of the lipid bilayer with cholesterol include structural properties, the lipid dynamics and mechanical properties of the bilayer. It was found that the lipid bilayer was condensed when it was embedded with cholesterol molecules. Addition of cholesterol in bilayer systems induced a smaller average surface area occupied by DPPC molecules, a more ordered hydrocarbon chains of DPPC molecules, and a thickened bilayer. The effects of cholesterol on dynamics properties of lipid bilayer were also observed as a decrease in the lateral diffusion coefficients for both cholesterol and DPPC in DPPC-­‐cholesterol mixture bilayer. Furthermore, lateral pressure profiles were calculated to look into the local stress distribution along the bilayer norm. It was found that cholesterol introduced extra contraction troughs in the profiles at the position under the head groups of DPPC, which explained the structural changes observed in the study. Bending moduli of the bilayer with and without cholesterol were estimated by calculating the splay modulus of pairs of each bilayer components. It was found that the involvement of cholesterol reduced the splay angles of each pair of bilayer component, resulting in a higher bending modulus of the structure.