Cholesterol Flip-Flop in Heterogeneous Membranes
Cholesterol Flip-Flop in Heterogeneous Membranes
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DOI：
10.1021/acs.jctc.8b00933
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发表时间：
2019-03-01
影响因子：
5.5
通讯作者：
Tieleman, D. Peter
中科院分区：
文献类型：
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作者：
Gu, Ruo-Xu;Baoukina, Svetlana;Tieleman, D. Peter
胆固醇是哺乳动物质膜中最丰富的分子。它在两个膜叶上的分布对于理解细胞如何工作至关重要。胆固醇跨双层运动（触发器）是影响其在膜中分布的关键过程。尽管进行了广泛的研究，胆固醇翻转的速率及其对膜横向异质性的依赖性仍然不确定。在这项工作中，我们使用原子分子动力学模拟对脂质横向分布不均匀的 DPPC:DOPC:胆固醇混合物中的自发胆固醇翻转事件进行采样。除了亚毫秒时间尺度的总体触发率之外，我们还发现局部环境对触发率有显着影响。我们讨论了在模拟中观察到的触发器事件的原子细节。
Cholesterol is the most abundant molecule in the plasma membrane of mammals. Its distribution across the two membrane leaflets is critical for understanding how cells work. Cholesterol trans-bilayer motion (flip-flop) is a key process influencing its distribution in membranes. Despite extensive investigations, the rate of cholesterol flip-flop and its dependence on the lateral heterogeneity of membranes remain uncertain. In this work, we used atomistic molecular dynamics simulations to sample spontaneous cholesterol flip-flop events in a DPPC:DOPC:cholesterol mixture with heterogeneous lateral distribution of lipids. In addition to an overall flip-flop rate at the time scale of sub-milliseconds, we identified a significant impact of local environment on flip-flop rate. We discuss the atomistic details of the flip-flop events observed in our simulations.