Lipid intermediates in membrane fusion: Formation, structure, and decay of hemifusion diaphragm
Lipid intermediates in membrane fusion: Formation, structure, and decay of hemifusion diaphragm
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DOI：
10.1016/s0006-3495(02)75274-0
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发表时间：
2002-11-01
影响因子：
3.4
通讯作者：
Kozlov, MM
中科院分区：
文献类型：
--
作者：
Kozlovsky, Y;Chernomordik, LV;Kozlov, MM
脂质双层融合被认为涉及形成局部半融合连接，称为融合柄。导致融合孔打开的后续融合阶段仍不清楚。最早的融合孔可能代表膜之间的双层连接，并可以直接从茎形成。或者，融合孔可以在单个双层中形成，称为半融合隔膜(HID)，由茎膨胀产生。为了分析茎膨胀的可能性，我们利用最近发展起来的弹性模型，从理论上研究了半融合的途径。我们发现，对于具有足够负的自发伸展的脂类来说，茎有扩展为HID的趋势，(J)高于代德(S)和lt；0。对于不同的实验相关膜构型，我们找到了自发张开的两个特征值。X和(J)Over Tide(S)**，确定HD维。假设自发张开在(J)超过波浪线(S)**<；(J)波浪线(S)和(J)波浪线(S)*的范围内，并对(J)波浪线(S)和(J)波浪线(S)**无限扩展，则HD有一个有限的平衡半径。在普通脂类的情况下，它不会自发融合，只有在外力拉开隔膜边缘的作用下才会形成HID。我们计算了HID半径与这个力的关系。为了解决融合孔形成的机制，我们分析了由于在变形的和松弛的部分脂单分子层之间建立横向平衡而在HD中出现的侧向张力的分布。我们发现，这种张力沿HID边缘集中，并达到足以破坏双层并形成融合孔的高值。我们的分析支持从半融合到融合孔的转变涉及茎的径向膨胀的假设。
Lipid bilayer fusion is thought to involve formation of a local hemifusion connection, referred to as a fusion stalk. The subsequent fusion stages leading to the opening of a fusion pore remain unknown. The earliest fusion pore could represent a bilayer connection between the membranes and could be formed directly from the stalk. Alternatively, fusion pore can form in a single bilayer, referred to as hemifusion diaphragm (HID), generated by stalk expansion. To analyze the plausibility of stalk expansion, we studied the pathway of hemifusion theoretically, using a recently developed elastic model. We show that the stalk has a tendency to expand into an HID for lipids with sufficiently negative spontaneous splay, (J) over tilde (s) < 0. For different experimentally relevant membrane configurations we find two characteristic values of the spontaneous splay. X and (J) over tilde (s)**, determining HD dimension. The HD is predicted to have a finite equilibrium radius provided that the spontaneous splay is in the range (J) over tilde (s)** < (J) over tilde (s) < (J) over tilde (s)*, and to expand infinitely for (J) over tilde (s) < (J) over tilde (s)**. In the case of common lipids, which do not fuse spontaneously, an HID forms only under action of an external force pulling the diaphragm rim apart. We calculate the dependence of the HID radius on this force. To address the mechanism of fusion pore formation, we analyze the distribution of the lateral tension emerging in the HD due to the establishment of lateral equilibrium between the deformed and relaxed portions of lipid monolayers. We show that this tension concentrates along the HID rim and reaches high values sufficient to rupture the bilayer and form the fusion pore. Our analysis supports the hypothesis that transition from a hemifusion to a fusion pore involves radial expansion of the stalk.