Cholesterol induces specific spatial and orientational order in cholesterol/phospholipid membranes.
Cholesterol induces specific spatial and orientational order in cholesterol/phospholipid membranes.
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DOI：
10.1371/journal.pone.0011162
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发表时间：
2010-06-17
期刊：
影响因子：
3.7
通讯作者：
Reigada R
中科院分区：
文献类型：
--
作者：
Martinez-Seara H;Róg T;Karttunen M;Vattulainen I;Reigada R
在脂质双层中，胆固醇促进液体有序相的形成，并能够形成横向有序结构，例如脂筏。虽然这些结构域在各种细胞过程中发挥着重要作用，但负责胆固醇特定排序和包装能力的精确原子水平机制仍未解决。我们的原子尺度分子动力学模拟表明，膜中的这种排序和相关堆积效应很大程度上是由胆固醇的分子结构造成的，这将胆固醇与其他甾醇区分开来。我们发现胆固醇分子更喜欢位于第二配位壳中，避免胆固醇-胆固醇直接接触，并与近端胆固醇分子形成三重对称排列。在较大距离处，横向三重组织被热波动破坏。对于结构不对称性较小的其他甾醇，三重排列显着丢失。我们得出结论，胆固醇分子在脂质膜中集体起作用。这是为什么只有当 Chol 浓度远高于 10 mol% 时才会出现液态有序相的主要原因，此时 Chol 分子的集体自组织会自发出现。集体排序过程需要特定的分子尺度特征，以解释为什么不同的甾醇具有非常不同的膜排序特性：Chol-Chol 组织中的三重对称性源于胆固醇平面外甲基，从而可以从不促进筏的甾醇中识别出促进筏的甾醇。
In lipid bilayers, cholesterol facilitates the formation of the liquid-ordered phase and enables the formation of laterally ordered structures such as lipid rafts. While these domains have an important role in a variety of cellular processes, the precise atomic-level mechanisms responsible for cholesterol's specific ordering and packing capability have remained unresolved. Our atomic-scale molecular dynamics simulations reveal that this ordering and the associated packing effects in membranes largely result from cholesterol's molecular structure, which differentiates cholesterol from other sterols. We find that cholesterol molecules prefer to be located in the second coordination shell, avoiding direct cholesterol-cholesterol contacts, and form a three-fold symmetric arrangement with proximal cholesterol molecules. At larger distances, the lateral three-fold organization is broken by thermal fluctuations. For other sterols having less structural asymmetry, the three-fold arrangement is considerably lost. We conclude that cholesterol molecules act collectively in lipid membranes. This is the main reason why the liquid-ordered phase only emerges for Chol concentrations well above 10 mol% where the collective self-organization of Chol molecules emerges spontaneously. The collective ordering process requires specific molecular-scale features that explain why different sterols have very different membrane ordering properties: the three-fold symmetry in the Chol-Chol organization arises from the cholesterol off-plane methyl groups allowing the identification of raft-promoting sterols from those that do not promote rafts.
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影响因子：
15
作者：
Marrink, Siewert J.;de Vries, Alex H.;Wassall, Stephen R.
通讯作者：
Wassall, Stephen R.
影响因子：
3.3
作者：
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影响因子：
3.4
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Höltje, HD
影响因子：
3.3
作者：
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通讯作者：
Vattulainen, Ilpo
影响因子：
3.4
作者：
Li, XM;Momsen, MM;Brown, RE
通讯作者：
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