Membrane mechanics as a probe of ion-channel gating mechanisms.
Membrane mechanics as a probe of ion-channel gating mechanisms.
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DOI：
10.1103/physreve.78.041901
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Phillips R
中科院分区：
文献类型：
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作者：
Reeves D;Ursell T;Sens P;Kondev J;Phillips R
跨膜离子通道在电场和膜张力等刺激下发生构象变化的细节仍存在争议。我们通过考虑构象变化如何在脂质双分子层中施加变形来解决这个问题。我们将重点放在电压门控通道中双层变形的作用上，因为我们假设这种变形在这种情况下以及对机械敏感的通道都是相关的。由于蛋白质构象的改变，我们预测脂质双分子层会发生变形，其特征自由能尺度为10kBT。这种自由能与总门控能量的电压相关部分相当，我们认为这些变形可能在门控的总体自由能预算中起重要作用。因此，通道活性将取决于机械膜参数，如张力和小叶厚度。我们进一步认为，任何通道周围的膜变形可以分为三种变形类型，它们表现出不同的机械敏感特性。最后，我们提供了理论框架，将门控过程中的构象变化与临界门控电压下的张力和小叶厚度依赖关系联系起来。这条研究路线表明，实验可以辨别由于通道门控而施加在膜上的主要变形，从而为刺激引起的通道变形提供线索。
The details of conformational changes undergone by transmembrane ion channels in response to stimuli, such as electric fields and membrane tension, remain controversial. We approach this problem by considering how the conformational changes impose deformations in the lipid bilayer. We focus on the role of bilayer deformations in the context of voltage-gated channels because we hypothesize that such deformations are relevant in this case as well as for channels that are explicitly mechanosensitive. As a result of protein conformational changes, we predict that the lipid bilayer suffers deformations with a characteristic free-energy scale of 10kBT. This free energy is comparable to the voltage-dependent part of the total gating energy, and we argue that these deformations could play an important role in the overall free-energy budget of gating. As a result, channel activity will depend upon mechanical membrane parameters such as tension and leaflet thickness. We further argue that the membrane deformation around any channel can be divided into three generic classes of deformation that exhibit different mechanosensitive properties. Finally, we provide the theoretical framework that relates conformational changes during gating to tension and leaflet thickness dependence in the critical gating voltage. This line of investigation suggests experiments that could discern the dominant deformation imposed upon the membrane as a result of channel gating, thus providing clues as to the channel deformation induced by the stimulus.