Multi-step formation of a hemifusion diaphragm for vesicle fusion revealed by all-atom molecular dynamics simulations.
Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipid clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
Department of Chemistry, National Central University, Jhong-Li City, Tao-Yuan County 32001, Taiwan. Electronic address: hhtsai@cc.ncu.edu.tw.
Hui-Hsu Gavin
HH
Tsai
Department of Chemistry, National Central University, Jhong-Li City, Tao-Yuan County 32001, Taiwan.
Che-Ming
CM
Chang
Department of Chemistry, National Central University, Jhong-Li City, Tao-Yuan County 32001, Taiwan.
Jian-Bin
JB
Lee
D000465:Algorithms; D002118:Calcium / Q000737:chemistry; D019295:Computational Biology; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008561:Membrane Fusion / Q000502:physiology*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010714:Phosphatidylethanolamines / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D053835:Unilamellar Liposomes; D014867:Water; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; D002118:Calcium
Energy landscape; Hemifusion diaphragm; Hemifusion diaphragm thinning; Membrane fusion; Multi-step event