Kozlovsky Yonathan, Kozlov Michael M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Biophys J. 2002 Feb;82(2):882-95. doi: 10.1016/S0006-3495(02)75450-7.
Membrane fusion proceeds via formation of intermediate nonbilayer structures. The stalk model of fusion intermediate is commonly recognized to account for the major phenomenology of the fusion process. However, in its current form, the stalk model poses a challenge. On one hand, it is able to describe qualitatively the modulation of the fusion reaction by the lipid composition of the membranes. On the other, it predicts very large values of the stalk energy, so that the related energy barrier for fusion cannot be overcome by membranes within a biologically reasonable span of time. We suggest a new structure for the fusion stalk, which resolves the energy crisis of the model. Our approach is based on a combined deformation of the stalk membrane including bending of the membrane surface and tilt of the hydrocarbon chains of lipid molecules. We demonstrate that the energy of the fusion stalk is a few times smaller than those predicted previously and the stalks are feasible in real systems. We account quantitatively for the experimental results on dependence of the fusion reaction on the lipid composition of different membrane monolayers. We analyze the dependence of the stalk energy on the distance between the fusing membranes and provide the experimentally testable predictions for the structural features of the stalk intermediates.
膜融合通过形成中间非双层结构进行。融合中间体的茎模型通常被认为可以解释融合过程的主要现象学。然而，就其目前的形式而言，茎模型存在一个挑战。一方面，它能够定性地描述膜的脂质组成对融合反应的调节。另一方面，它预测茎能量的值非常大，以至于在生物学上合理的时间范围内，膜无法克服与融合相关的能量障碍。我们提出了一种新的融合茎结构，解决了该模型的能量危机。我们的方法基于茎膜的组合变形，包括膜表面的弯曲和脂质分子烃链的倾斜。我们证明，融合茎的能量比之前预测的小几倍，并且茎在实际系统中是可行的。我们定量地解释了融合反应对不同膜单层脂质组成依赖性的实验结果。我们分析了茎能量对融合膜之间距离的依赖性，并为茎中间体的结构特征提供了可通过实验检验的预测。
