Molecular simulation of rapid translocation of cholesterol, diacylglycerol, and ceramide in model raft and nonraft membranes

被引:78
作者
Bennett, W. F. Drew
Tieleman, D. Peter [1 ]
机构
[1] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
flip-flop; molecular dynamics; lipid bilayer; free energy; desorption; lipid second-messenger; PARTICLE MESH EWALD; TRANSBILAYER MOVEMENT; LIPID RAFTS; FLIP-FLOP; DYNAMICS SIMULATIONS; UNILAMELLAR VESICLES; CELL-MEMBRANES; FATTY-ACIDS; TRANSPORT; BILAYER;
D O I
10.1194/jlr.M022491
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The translocation of lipids across membranes (flip-flop) is an important biological process. Slow exchange on a physiological timescale allows the creation of asymmetric distributions of lipids across cellular membranes. The location of lipids and their rate of exchange have important biological consequences, especially for lipids involved in cellular signaling. We investigated the translocation of cholesterol, ceramide, and diacylglycerol in two model bilayers using molecular dynamics simulations. We estimate half times for flip-flop for cholesterol, diacylglycerol, and ceramide of 20 mu s, 30 mu s, and 10 ms in a POPC bilayer, compared with approximately 30 min, 30 ms, and 30 s in a model raft bilayer (1:1:1 PSM, POPC, and cholesterol). Cholesterol has a large (54 kJ/mol) free energy of exchange between the POPC and raft bilayer, and therefore, it strongly prefers the more ordered and rigid raft bilayer over the more liquid POPC bilayer. Ceramide and diacylglycerol have relatively small free energies of exchange, suggesting nearly equal preference for both bilayers. This unexpected result may have implications for ceramide and diacylglycerol signaling and membrane localization.-Bennett, W. F. D, and D. P. Tieleman. Molecular simulation of rapid translocation of cholesterol, diacylglycerol, and ceramide in model raft and nonraft membranes. J. Lipid Res. 2012. 53: 421-429.
引用
收藏
页码:421 / 429
页数:9
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