How Cholesterol Tilt Modulates the Mechanical Properties of Saturated and Unsaturated Lipid Membranes
How Cholesterol Tilt Modulates the Mechanical Properties of Saturated and Unsaturated Lipid Membranes
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DOI：
10.1021/jp3122006
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发表时间：
2013-02-28
影响因子：
3.3
通讯作者：
Harries, Daniel
中科院分区：
文献类型：
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作者：
Khelashvili, George;Harries, Daniel
尽管在了解胆固醇对脂质膜各种特性的影响方面取得了很大进展，但其在分子水平上决定双分子层弹性的机制作用尚未完全解决。事实上，迄今为止，驱动实验检测到的含有胆固醇的饱和和不饱和脂质双分子层特性差异的分子机制仍不清楚。通过从混合脂质-胆固醇膜的原子分子动力学模拟中量化胆固醇取向自由度，我们从胆固醇倾斜和张开的角度解决了这个问题。根据模拟中胆固醇和脂质分子方向的波动，我们提取了胆固醇分子和碳氢脂质尾部的倾斜模量和张开模量。这进一步使我们能够估计这些模态对膜对弹性变形的响应的贡献。我们发现倾斜和张开变形对混合脂质膜的整体弹性有重要贡献，并且它们可以解释液体有序鞘磷脂(SM)/胆固醇双分子层和液体二油酰磷脂(DOPC)/胆固醇双分子层之间实验建立的差异。这些发现强调了倾斜模量和张开模量的重要性，这些模量来源于相对易于计算的模拟，是定量表征混合脂-胆固醇双层力学特性的有用指标。
Although there have been great advances in understanding the effect of cholesterol on various properties of lipid membranes, its mechanistic role in determining the elasticity of bilayers at the molecular level is not fully resolved. Indeed, to date the molecular mechanisms that drive the experimentally detected differences in properties of saturated and unsaturated lipid bilayers that contain cholesterol remain unclear. By quantifying the cholesterol orientational degrees of freedom from atomistic molecular dynamics simulations of mixed lipid-cholesterol membranes, we address this question from the perspective of cholesterol tilt and splay. Following the fluctuations in orientations of cholesterol and of lipid molecules in simulations, we have extracted tilt and splay moduli both for cholesterol molecules and hydrocarbon lipid tails. This has further allowed us to estimate the contributions of these modes to the response of membranes to elastic deformations. We find that tilt and splay deformations importantly contribute to the overall elasticity of the mixed lipid membranes, and that they can account for the experimentally established differences between the liquid ordered sphingomyelin (SM)/cholesterol bilayers and fluid dioleoylphosphocholine (DOPC)/cholesterol bilayers. These findings underscore the importance of tilt and splay moduli, derived from simulations with relative computational ease, as useful metrics for quantitatively characterizing the mechanical properties of mixed lipid-cholesterol bilayers.