Cholesterol-Induced Modifications in Lipid Bilayers: A Simulation Study Export

@article{citeulike:3368135, abstract = {We present analysis of new configurational bias Monte Carlo and molecular dynamics simulation data for bilayers of dipalmitoyl phosphatidyl choline and cholesterol for dipalmitoyl phosphatidyl choline:cholesterol ratios of 24:1, 47:3, 11.5:1, 8:1, 7:1, 4:1, 3:1, 2:1, and 1:1, using long molecular dynamics runs and interspersed configurational bias Monte Carlo to ensure equilibration and enhance sampling. In all cases with cholesterol concentrations above 12.5\% the area per molecule of the heterogeneous membrane varied linearly with cholesterol fraction. By extrapolation to pure cholesterol, we find the cross-sectional area of cholesterol in these mixtures is \~{}22.3 A2. From the slope of the area/molecule relationship, we also find that the phospholipid in these mixtures is in a liquid ordered state with an average cross-sectional area per lipid of 50.7 A2, slightly above the molecular area of a pure phospholipid gel. For lower concentrations of cholesterol, the molecular area rises above the straight line, indicating the "melting" of at least some of the phospholipid into a fluid state. Analysis of the lateral distribution of cholesterol molecules in the leaflets reveals peaks in radial distributions of cholesterols at multiples of \~{}5 A. These peaks grow in size as the simulation progresses, suggesting a tendency for small subunits of one lipid plus one cholesterol, hydrogen bonded together, to act as one composite particle, and perhaps to aggregate with other composites. Our results are consistent with experimentally observed effects of cholesterol, including the condensation effect of cholesterol in phospholipid monolayers and the tendency of cholesterol-rich domains to form in cholesterol-lipid bilayers. We are continuing to analyze this tendency on longer timescales and for larger bilayer patches.}, author = {Chiu, S. W. and Jakobsson, Eric and Mashl, Jay R. and Scott, Larry H.}, citeulike-article-id = {3368135}, citeulike-linkout-0 = {http://www.biophysj.org/cgi/content/abstract/83/4/1842}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12324406}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12324406}, day = {1}, journal = {Biophys. J.}, keywords = {membrane}, month = {October}, number = {4}, pages = {1842--1853}, posted-at = {2008-10-03 06:35:29}, priority = {2}, title = {Cholesterol-Induced Modifications in Lipid Bilayers: A Simulation Study}, url = {http://www.biophysj.org/cgi/content/abstract/83/4/1842}, volume = {83}, year = {2002} }

TY - JOUR ID - citeulike:3368135 L3 - citeulike-article-id:3368135 N2 - We present analysis of new configurational bias Monte Carlo and molecular dynamics simulation data for bilayers of dipalmitoyl phosphatidyl choline and cholesterol for dipalmitoyl phosphatidyl choline:cholesterol ratios of 24:1, 47:3, 11.5:1, 8:1, 7:1, 4:1, 3:1, 2:1, and 1:1, using long molecular dynamics runs and interspersed configurational bias Monte Carlo to ensure equilibration and enhance sampling. In all cases with cholesterol concentrations above 12.5% the area per molecule of the heterogeneous membrane varied linearly with cholesterol fraction. By extrapolation to pure cholesterol, we find the cross-sectional area of cholesterol in these mixtures is ~22.3 A2. From the slope of the area/molecule relationship, we also find that the phospholipid in these mixtures is in a liquid ordered state with an average cross-sectional area per lipid of 50.7 A2, slightly above the molecular area of a pure phospholipid gel. For lower concentrations of cholesterol, the molecular area rises above the straight line, indicating the "melting" of at least some of the phospholipid into a fluid state. Analysis of the lateral distribution of cholesterol molecules in the leaflets reveals peaks in radial distributions of cholesterols at multiples of ~5 A. These peaks grow in size as the simulation progresses, suggesting a tendency for small subunits of one lipid plus one cholesterol, hydrogen bonded together, to act as one composite particle, and perhaps to aggregate with other composites. Our results are consistent with experimentally observed effects of cholesterol, including the condensation effect of cholesterol in phospholipid monolayers and the tendency of cholesterol-rich domains to form in cholesterol-lipid bilayers. We are continuing to analyze this tendency on longer timescales and for larger bilayer patches. IS - 4 JF - Biophys. J. EP - 1853 TI - Cholesterol-Induced Modifications in Lipid Bilayers: A Simulation Study VL - 83 SP - 1842 KW - membrane AU - Chiu, SW AU - Jakobsson, Eric AU - Mashl, Jay AU - Scott, Larry PY - 2002/10/01/ UR - http://www.biophysj.org/cgi/content/abstract/83/4/1842 ER -