Department of Chemical and Biological Engineering, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104, United States.
Department of Chemical and Biological Engineering, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104, United States.
Biochim Biophys Acta Biomembr. 2018 Jul;1860(7):1452-1459. doi: 10.1016/j.bbamem.2018.04.007. Epub 2018 Apr 22.
Molecular dynamics simulations of a solvent-free coarse-grained lipid model are used to characterize the mechanisms by which lipid-bilayer hemifusion diaphragm (HD) intermediates relax, across a range of global compositions of negative intrinsic curvature (NIC) lipids and neutral-curvature lipids. At low concentrations of NIC lipids, rapid fission produces a double bilayer end state through a lateral diffusion-based mechanism enabled by spontaneous rim-pore defects. At moderately higher NIC lipid concentrations, rim pores are absent and stable leaflet three-junctions persist, revealing an HD relaxation mechanism entirely reliant on lipid flip-flop, and end states that are either stable fusion pores or stable HD's. These fusogenic systems exhibit dynamics highly dependent on NIC lipid concentration via an underlying sensitivity of flip-flop rates for neutral lipids on NIC lipid concentration. This work illustrates that HD dynamics may be altered through regulation of lipid composition in the immediate three-junction region. This work further highlights the potential role of flippases in biological fusion and the importance of lipid composition on fusion dynamics.
无溶剂粗粒脂质模型的分子动力学模拟用于描述脂质双层半融合膜（HD）中间体在不同的负向固有曲率（NIC）脂质和中性曲率脂质的全局组成范围内的弛豫机制。在 NIC 脂质浓度较低时，快速裂变通过自发的边缘孔缺陷所支持的基于侧向扩散的机制产生双层末端状态。在稍高的 NIC 脂质浓度下，边缘孔不存在，稳定的小叶三联体持续存在，揭示了一种完全依赖于脂质翻转的 HD 弛豫机制，以及稳定的融合孔或稳定的 HD 的末端状态。这些融合系统的动力学高度依赖于 NIC 脂质浓度，这是由于中性脂质的翻转速率对 NIC 脂质浓度具有潜在的敏感性。这项工作表明，HD 的动力学可以通过调节紧邻三联体区域的脂质组成来改变。这项工作进一步强调了翻转酶在生物融合中的潜在作用以及脂质组成对融合动力学的重要性。
