Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala 75124, Sweden.
Departments of Molecular Physiology and Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, United States.
J Phys Chem Lett. 2020 Sep 3;11(17):7190-7196. doi: 10.1021/acs.jpclett.0c01778. Epub 2020 Aug 19.
Enveloped viruses infect cells via fusion between the viral envelope and a cellular membrane. This membrane fusion process is driven by viral proteins, but slow stochastic protein activation dominates the fusion kinetics, making it challenging to probe the role of membrane mechanics in viral entry directly. Furthermore, many changes to the interacting membranes alter the curvature, deformability, and spatial organization of membranes simultaneously. We have used bilayer-coated silica nanoparticles to restrict the deformability of lipid membranes in a controllable manner. The single-event kinetics for fusion of influenza virus to coated nanoparticles permits independent testing of how the membrane curvature and deformability control the free energy barriers to fusion. Varying the free energy of membrane deformation, but not membrane curvature, causes a corresponding response in the fusion kinetics and fusion protein stoichiometry. Thus, the main free energy barrier to lipid mixing by influenza virus is controlled by membrane deformability and not the initial membrane curvature.
包膜病毒通过病毒包膜与细胞膜之间的融合感染细胞。这个膜融合过程由病毒蛋白驱动，但缓慢的随机蛋白激活主导融合动力学，使得直接探测膜力学在病毒进入中的作用具有挑战性。此外，相互作用的膜的许多变化会同时改变膜的曲率、变形性和空间组织。我们使用双层涂覆的硅纳米颗粒以可控的方式限制脂质膜的变形性。流感病毒与涂覆纳米颗粒融合的单事件动力学允许独立测试膜曲率和变形性如何控制融合的自由能障碍。改变膜变形的自由能，而不是膜曲率，会导致融合动力学和融合蛋白计量比相应的响应。因此，流感病毒引起的脂质混合的主要自由能障碍由膜变形性控制，而不是初始膜曲率。
