Determination of Free Energy Barriers to Initial Fusion of Vesicles

Abstract

The fusion of two vesicles is studied by means of molecular dynamics simulations using coarse-grained lipid models. We use the umbrella sampling method to determine the potential of mean force as a function of the distance between the center of mass of two vesicles. The free energy barrier to the initial fusion step between two vesicles is determined from the peak in the PMF curve calculated at a center of mass distance just prior to the initial fusion step. The two CG lipid models used were the original model by Marrink, de Vries, and Mark (J. Phys. Chem. B 2004, 108,750) and its recently improved and extended version, the MARTINI model. We find that the free energy barrier for the initial fusion event varies by more than an order of magnitude between the two models. The source of the difference is found in the greater repulsive character of the interaction between the hydrophobic tail particles and the charged head-group particles in the MARTINI model compared to the older model. This interaction results in the lipid tails being confined to the hydrophobic region of the vesicle to a greater extent and the splay of the lipid tails being limited. These factors reduce the probability of triggering an initial fusion event.