Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers: a molecular dynamics study

Abstract

Cholesterol molecules were put into a computer-modeled hydrated bilayer of dimyristoyl phosphatidyl choline molecules, and molecular dynamics simulations were run to characterize the effect of this important molecule on membrane structure and dynamics. The effect was judged by observing differences in order parameters, tilt angles, and the fraction of gauche bonds along the hydrocarbon chains between lipids adjacent to cholesterol molecules and comparing them with those further away. It was observed that cholesterol causes an increase in the fraction of trans dihedrals and motional ordering of chains close to the rigid steroid ring system with a decrease in the kink population. The hydrogen-bonding interactions between cholesterol and lipid molecules were determined from radial distribution calculations and showed the cholesterol hydroxyl groups either solvated by water, or forming hydrogen bond contacts with the oxygens of lipid carbonyl and phosphate groups. The dynamics and conformation of the cholesterol molecules were investigated and it was seen that they had a smaller tilt with respect to the bilayer normal than the lipid chains and furthermore that the hydrocarbon tail of the cholesterol was conformationally flexible.

Cholesterol-Induced Interfacial Area Condensations of Galactosylceramides and Sphingomyelins with Identical Acyl Chains

“…Hence, it is clear that the extent to which cholesterol can reduce the cross-sectional areas of sphingolipids and phospholipids is critically linked to what might otherwise seem to be subtle structural differences. Interestingly, recent molecular dynamics computer simulations indicate that cholesterol does produce more trans dihedrals in the sn-1 chain than in the sn-2 chain of dimyristoyl-PC (Robinson et al, 1995).…”

Co-delivery of Doxorubicin and PSC 833 (Valspodar) by Stealth Nanoliposomes for Efficient Overcoming of Multidrug Resistance

“…Incorporation of higher Chol concentration in liposomal formulations increased the PSC 833 release rate. The planar and rigid ring system of Chol is thought to reside in outer layer part of the fatty acyl chain region where it tends to restrict the motion of chains in liquid crystalline bilayers (55,56) which may increase tendency of PSC 833 to partition in the release medium. We have previously reported phospholipids concentration-dependent drug release from liposomes (28).…”

Molecular Modelling of Biological Membranes: Structure and Permeation Properties

“…The rigid steroid ring system of the cholesterol molecules affects the conformations of the acyl chains, and tends to increase the population of trans conformations and decrease the free-volume fraction. Cholesterol contains one hydroxyl group, which gives this otherwise hydrophobic compound its hydrophilic character and ability to partition in hydrogen-bonding, with water molecules or with the lipid carbonyl and phosphate groups [138]. Simulations further show that the introduction of cholesterol allows for a broader distribution of P-N angles in the lipid head groups.…”