title: Molecular dynamics simulations of lipid vesicle fusion in atomic detail.
abstract: The fusion of a membrane-bounded vesicle with a target membrane is a key step in intracellular trafficking, exocytosis, and drug delivery. Molecular dynamics simulations have been used to study the fusion of small unilamellar vesicles composed of a dipalmitoyl-phosphatidylcholine (DPPC)/palmitic acid 1:2 mixture in atomic detail. The simulations were performed at 350-370 K and mimicked the temperature- and pH-induced fusion of DPPC/palmitic acid vesicles from experiments by others. To make the calculations computationally feasible, a vesicle simulated at periodic boundary conditions was fused with its periodic image. Starting from a preformed stalk between the outer leaflets of the vesicle and its periodic image, a hemifused state formed within 2 ns. In one out of six simulations, a transient pore formed close to the stalk, resulting in the mixing of DPPC lipids between the outer and the inner leaflet. The hemifused state was (meta)stable on a timescale of up to 11 ns. Forcing a single lipid into the interior of the hemifusion diaphragm induced the formation and expansion of a fusion pore on a nanosecond timescale. This work opens the perspective to study a wide variety of mesoscopic biological processes in atomic detail.
authors: Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
authors: Volker
authors: V
authors: Knecht
authors: Siewert-Jan
authors: SJ
authors: Marrink
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008560:Membrane Fluidity; D008561:Membrane Fusion; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D019308:Palmitic Acid / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D019308:Palmitic Acid