BIOPHYSICAL THEORY AND MODELING |
Molecular dynamics simulations of lipid vesicle fusion in
atomic detail
Volker Knecht 1 and Siewert Jan Marrink 2*
1 Max Planck Institute of Colloids and Interfaces
14424 Potsdam, Germany
2 University of Groningen
* To whom correspondence should be addressed. E-mail: s.j.marrink{at}rug.nl.
Submitted on December 22, 2006
Revised on January 15, 2007
Accepted on 12 February 2007
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Abstract |
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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 (PA) 1:2 mixture in atomic detail. The simulations were performed at 350 - 370K and mimicked the temperature- and pH-induced fusion of DPPC/PA vesicles in experiments by Zellmer et al.. 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.
Key Words:
computer modelling, exocytosis, fatty acid, hemifusion, membrane fusion, stalk
