Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, Room LC-501B, New York, NY, USA.
Chem Phys Lipids. 2013 Apr;169:113-23. doi: 10.1016/j.chemphyslip.2012.12.006. Epub 2013 Jan 3.
Serving as a crucial component of mammalian cells, cholesterol critically regulates the functions of biomembranes. This review focuses on a specific property of cholesterol and other sterols: the tilt modulus χ that quantifies the energetic cost of tilting sterol molecules inside the lipid membrane. We show how χ is involved in determining properties of cholesterol-containing membranes, and detail a novel approach to quantify its value from atomistic molecular dynamics (MD) simulations. Specifically, we link χ with other structural, thermodynamic, and mechanical properties of cholesterol-containing lipid membranes, and delineate how this useful parameter can be obtained from the sterol tilt probability distributions derived from relatively small-scale unbiased MD simulations. We demonstrate how the tilt modulus quantitatively describes the aligning field that sterol molecules create inside the phospholipid bilayers, and we relate χ to the bending rigidity of the lipid bilayer through effective tilt and splay energy contributions to the elastic deformations. Moreover, we show how χ can conveniently characterize the "condensing effect" of cholesterol on phospholipids. Finally, we demonstrate the importance of this cholesterol aligning field to the proper folding and interactions of membrane peptides. Given the relative ease of obtaining the tilt modulus from atomistic simulations, we propose that χ can be routinely used to characterize the mechanical properties of sterol/lipid bilayers, and can also serve as a required fitting parameter in multi-scaled simulations of lipid membrane models to relate the different levels of coarse-grained details.
胆固醇作为哺乳动物细胞的重要组成部分，对生物膜的功能起着关键的调节作用。本综述聚焦于胆固醇和其他固醇的一个特性：倾斜模量 χ，它量化了固醇分子在脂质膜内倾斜的能量成本。我们展示了 χ 如何参与决定含胆固醇膜的性质，并详细介绍了一种从原子分子动力学（MD）模拟中定量计算其值的新方法。具体来说，我们将 χ 与含胆固醇脂质膜的其他结构、热力学和力学性质联系起来，并详细说明了如何从相对小规模的无偏 MD 模拟中得出的固醇倾斜概率分布中获得这个有用的参数。我们证明了倾斜模量如何定量描述固醇分子在磷脂双分子层内产生的对齐场，并且我们通过有效倾斜和伸展能对弹性变形的贡献将 χ 与脂质双层的弯曲刚度联系起来。此外，我们还展示了 χ 如何方便地描述胆固醇对磷脂的“浓缩效应”。最后，我们证明了这种胆固醇对齐场对膜肽正确折叠和相互作用的重要性。鉴于从原子模拟中获得倾斜模量相对容易，我们建议 χ 可以常规用于表征固醇/脂质双层的力学性质，并且还可以作为脂质膜模型的多尺度模拟中必需的拟合参数，以将不同的粗粒度细节水平联系起来。
