title: Coarse-grained molecular dynamics study of membrane fusion: Curvature effects on free energy barriers along the stalk mechanism.
abstract: The effects of membrane curvature on the free energy barrier for membrane fusion have been investigated using coarse-grained molecular dynamics (CG-MD) simulations, assuming that fusion takes place through a stalk intermediate. Free energy barriers were estimated for stalk formation as well as for fusion pore formation using the guiding potential method. Specifically, the three different geometries of two apposed membranes were considered: vesicle-vesicle, vesicle-planar, and planar-planar membranes. The free energy barriers for the resulting fusion were found to depend importantly on the fusing membrane geometries; the lowest barrier was obtained for vesicular membranes. Further, lipid sorting was observed in fusion of the mixed membranes of dimyristoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine (DOPE). Specifically, DOPE molecules were found to assemble around the stalk to support the highly negative curved membrane surface. A consistent result for lipid sorting was observed when a simple continuum model (CM) was used, where the Helfrich energy and mixing entropy of the lipids were taken into account. However, the CM predicts a much higher free energy barrier than found using CG-MD. This discrepancy originates from the conformational changes of lipids, which were not considered in the CM. The results of the CG-MD simulations reveal that a large conformational change in the lipid takes place around the stalk region, which results in a reduction of free energy barriers along the stalk mechanism of membrane fusion.
authors.affiliation: Department of Applied Chemistry, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kawamoto
authors.affiliation: Institute for Computational Molecular Science, Temple University, SERC Building 1925 North 12th Street, Philadelphia, Pennsylvania 19122, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Department of Applied Chemistry, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shinoda
mesh_terms: D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D004134:Dimyristoylphosphatidylcholine