Ion-induced defect permeation of lipid membranes.
Ion-induced defect permeation of lipid membranes.
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DOI：
10.1016/j.bpj.2013.12.027
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发表时间：
2014-02
影响因子：
3.4
通讯作者：
I. Vorobyov;Timothy E Olson;J. H. Kim;R. Koeppe;O. Andersen;T. Allen
中科院分区：
文献类型：
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作者：
I. Vorobyov;Timothy E Olson;J. H. Kim;R. Koeppe;O. Andersen;T. Allen
我们利用原子模拟和电生理记录探索了非催化膜离子渗透的机理。自20世纪60年代以来，膜电荷传输的溶解-扩散机制一直占主导地位，尽管实验观察不一致，并且没有考虑到脂双分子层的灵活反应。我们发现碱金属离子、氯离子和带电的精氨酸侧链类似物的直接脂双层转移是通过离子诱导的缺陷机制发生的。与以前的一些建议相反，精氨酸类似物经历了一个很大的自由能势垒，非常类似于Na+，K+和Cl-的势垒。我们的模拟表明，由于离子运动引起的膜扰动是解释渗透过程的中心，导致自由能和扩散系数曲线显示几乎不依赖于离子化学和电荷，尽管水化能和膜的偶极电势范围很大。结果表明，膜的渗透率在大小和选择性方面与实验结果是半定量一致的。我们的结论是，离子诱导的缺陷介导的渗透可能与瞬时孔竞争，成为非催化离子渗透的主要机制，为一系列膜活性多肽和蛋白质的作用提供了新的理解。
We have explored the mechanisms of uncatalyzed membrane ion permeation using atomistic simulations and electrophysiological recordings. The solubility-diffusion mechanism of membrane charge transport has prevailed since the 1960s, despite inconsistencies in experimental observations and its lack of consideration for the flexible response of lipid bilayers. We show that direct lipid bilayer translocation of alkali metal cations, Cl–, and a charged arginine side chain analog occurs via an ion-induced defect mechanism. Contrary to some previous suggestions, the arginine analog experiences a large free-energy barrier, very similar to those for Na+, K+, and Cl–. Our simulations reveal that membrane perturbations, due to the movement of an ion, are central for explaining the permeation process, leading to both free-energy and diffusion-coefficient profiles that show little dependence on ion chemistry and charge, despite wide-ranging hydration energies and the membrane's dipole potential. The results yield membrane permeabilities that are in semiquantitative agreement with experiments in terms of both magnitude and selectivity. We conclude that ion-induced defect-mediated permeation may compete with transient pores as the dominant mechanism of uncatalyzed ion permeation, providing new understanding for the actions of a range of membrane-active peptides and proteins.