Department of Physiology, University of Wisconsin Madison, Madison, WI 53706, USA.
J Membr Biol. 2009 Oct;231(2-3):101-15. doi: 10.1007/s00232-009-9209-x. Epub 2009 Oct 29.
Membranes fuse by forming highly curved intermediates, culminating in structures described as fusion pores. These hourglass-like figures that join two fusing membranes have high bending energies, which can be estimated using continuum elasticity models. Fusion pore bending energies depend strongly on shape, and the present study developed a method for determining the shape that minimizes bending energy. This was first applied to a fusion pore modeled as a single surface and then extended to a more realistic model treating a bilayer as two monolayers. For the two-monolayer model, fusion pores were found to have metastable states with energy minima at particular values of the pore diameter and bilayer separation. Fusion pore energies were relatively insensitive to membrane thickness but highly sensitive to spontaneous curvature and membrane asymmetry. With symmetrical bilayers and monolayer spontaneous curvatures of -0.1 nm(-1) (a typical value) separated by 6 nm (closest distance determined by repulsive hydration forces), fusion pore formation required 43-65 kT. The pore radius of approximately 2.25 nm fell within the range estimated from conductance measurements. With bilayer separation >6 nm, fusion pore formation required less energy, suggesting that protein scaffolds can promote fusion by bending membranes toward one another. With nonzero spontaneous monolayer curvature, the shape that minimized the energy change during fusion pore formation differed from the shape that minimized its energy after it formed. Thus, a nascent fusion pore will relax spontaneously to a new shape, consistent with the experimentally observed expansion of nascent fusion pores during viral fusion.
膜融合通过形成高度弯曲的中间体来实现，最终形成融合孔结构。这些连接两个融合膜的沙漏状结构具有较高的弯曲能，可以使用连续弹性模型进行估计。融合孔弯曲能强烈依赖于形状，本研究开发了一种确定最小化弯曲能的形状的方法。该方法首先应用于单表面建模的融合孔，然后扩展到更现实的双层膜作为两个单层膜模型。对于双层膜模型，发现融合孔具有亚稳态，其能量最小值出现在特定的孔径和双层分离值处。融合孔能量对膜厚度相对不敏感，但对自发曲率和膜不对称性高度敏感。对于对称双层膜和单层自发曲率为-0.1nm^(-1)（典型值），分离距离为 6nm（由排斥水合力决定的最近距离），融合孔形成需要 43-65kT。孔半径约为 2.25nm，落在电导测量估计的范围内。当双层分离距离大于 6nm 时，融合孔形成所需的能量更少，这表明蛋白质支架可以通过使膜彼此弯曲来促进融合。对于非零自发单层曲率，在融合孔形成过程中最小化能量变化的形状与形成后最小化其能量的形状不同。因此，新生的融合孔将自发松弛到新的形状，这与实验观察到的病毒融合过程中新生融合孔的扩张一致。
