Biomechanics and Biomaterials Laboratory, Department of Applied Mechanics, Beijing Institute of Technology, Beijing 100081, China.
Soft Matter. 2018 Jun 27;14(25):5277-5282. doi: 10.1039/c8sm00644j.
Membrane fusion is a fundamental biological process that lies at the heart of enveloped virus infection, synaptic signaling, intracellular vesicle trafficking, gamete fertilization, and cell-cell fusion. Membrane fusion is initiated as two apposed membranes merge to a single bilayer called a hemifusion diaphragm. It is believed that the contents of the two fusing membranes are released through a fusion pore formed at the hemifusion diaphragm, and yet another possible pathway has been proposed in which an undefined pore may form outside the hemifusion diaphragm at the apposed membranes, leading to the so-called leaky fusion. Here, we performed all-atom molecular dynamics simulations to study the evolution of the hemifusion diaphragm structure with various lipid compositions. We found that the lipid cholesterol decreased water penetrability to inhibit leakage pore formation. Biochemical leakage experiments support these simulation results. This study may shed light on the underlying mechanism of the evolution pathways of the hemifusion structure, especially the understanding of content leakage during membrane fusion.
膜融合是一种基本的生物学过程，它是包膜病毒感染、突触信号传递、细胞内囊泡运输、配子受精和细胞融合的核心。膜融合是由两个相邻的膜融合成一个称为半融合膈膜的单层双层开始的。人们认为，两个融合膜的内容物是通过在半融合膈膜处形成的融合孔释放的，但另一种可能的途径是，在相邻的膜处，半融合膈膜之外可能形成一个未定义的孔，导致所谓的渗漏融合。在这里，我们进行了全原子分子动力学模拟，以研究具有不同脂质组成的半融合膈膜结构的演变。我们发现脂质胆固醇降低了水的渗透性，从而抑制了渗漏孔的形成。生化渗漏实验支持这些模拟结果。这项研究可能揭示了半融合结构演变途径的潜在机制，特别是在理解膜融合过程中的内容物渗漏方面。
