Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, United States.
J Phys Chem B. 2013 Feb 28;117(8):2411-21. doi: 10.1021/jp3122006. Epub 2013 Jan 30.
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.
尽管人们在理解胆固醇对脂质膜各种性质的影响方面已经取得了很大的进展，但它在确定双层膜弹性方面的分子作用在分子水平上仍未得到完全解决。事实上，迄今为止，驱动含有胆固醇的饱和和不饱和脂质双层膜性质实验检测到的差异的分子机制仍不清楚。通过对混合脂质-胆固醇膜的原子分子动力学模拟来量化胆固醇的取向自由度，我们从胆固醇倾斜和展开的角度来解决这个问题。在模拟中胆固醇和脂质分子取向的波动之后，我们提取了胆固醇分子和碳氢脂质尾部的倾斜和展开模量。这进一步使我们能够估计这些模式对膜对弹性变形的响应的贡献。我们发现倾斜和展开变形对混合脂质膜的整体弹性有重要贡献，并且它们可以解释实验确定的液体有序神经鞘磷脂 (SM)/胆固醇双层膜和流体二油酰基磷酸胆碱 (DOPC)/胆固醇双层膜之间的差异。这些发现强调了从相对计算容易的模拟中得出的倾斜和展开模量作为定量描述混合脂质-胆固醇双层膜力学性质的有用指标的重要性。
