Flip-Flop of Oleic Acid in a Phospholipid Membrane: Rate and Mechanism
Flip-Flop of Oleic Acid in a Phospholipid Membrane: Rate and Mechanism
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DOI：
10.1021/jp508163e
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发表时间：
2014-11-13
影响因子：
3.3
通讯作者：
Pohorille, Andrew
中科院分区：
文献类型：
--
作者：
Wei, Chenyu;Pohorille, Andrew
借助分子动力学模拟，在几微秒的时间尺度上研究了以两种不同浓度溶解在由1-棕榈酰-2-油酰-SN-甘油-3-磷酸胆碱制成的膜中的质子化油酸分子的触发。直接，单分子触发器事件观察到在这个时间尺度上，和触发器速率估计为0.20.3 μ S-1。当油酸分子在翻转过程中向双层的中心移动时，它们经历渐进的、相关的平移和旋转运动。还观察到两个氢键结合的油酸分子的罕见的双翻转事件。一个二维的自由能表面的油酸分子的平移和旋转的自由度，并确定在此表面上的最小能量路径。在双层的中心发现了一个类似于4.2千卡/摩尔的触发势垒。一个二维扩散模型被发现提供了一个很好的描述的触发器过程。快速的翻转速率支持了脂肪酸在没有转运蛋白帮助的情况下渗透膜的提议。它还表明，解吸，而不是触发器是脂肪酸通过膜运输的限速步骤。触发器率的祖先细胞系统的进化的关系进行了讨论。
Flip-flop of protonated oleic acid molecules dissolved at two different concentrations in membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine is studied with the aid of molecular dynamics simulations at a time scale of several microseconds. Direct, single-molecule flip-flop events are observed at this time scale, and the flip-flop rate is estimated at 0.20.3 mu s1. As oleic acid molecules move toward the center of the bilayer during flip-flop, they undergo gradual, correlated translational, and rotational motion. Rare, double-flipping events of two hydrogen-bonded oleic acid molecules are also observed. A two-dimensional free energy surface is obtained for the translational and rotational degree of freedom of the oleic acid molecule, and the minimum energy path on this surface is determined. A barrier to flip-flop of similar to 4.2 kcal/mol is found at the center of the bilayer. A two-dimensional diffusion model is found to provide a good description of the flip-flop process. The fast flip-flop rate lends support to the proposal that fatty acids permeate membranes without assistance of transport proteins. It also suggests that desorption rather than flip-flop is the rate-limiting step in fatty acid transport through membranes. The relation of flip-flop rates to the evolution of ancestral cellular systems is discussed.