Molecular dynamics study of lipid based vesicle fission

Together with vesicle fusion and budding, vesicle fission plays an important role in intracellular traffic. Vesicle fission is known to take place in different ways, either or not instigated by proteins. However, as at a molecular level the dynamics of the cell membrane and the working mechanisms of proteins cannot be readily asserted experimentally, many different hypotheses exist to predict and explain these processes. Therefore, we use coarse grained molecular dynamics simulations to elucidate the fission mechanism of vesicles, where we focus on possible mechanisms in the absence of proteins. Two distinct routes are considered that are both based on an asymmetry of the lipid distribution in the membrane. I n the first mechanism, the two types of lipids are equally distributed over both leaflets of the membrane. However, phase separation of the lipids within both leaflets results in domains which form buds that can split off. I n the second mechanism, the asymmetry consists either of a difference in composition between the two monolayers of the membrane or of a difference between the vesicle interior and exterior. This difference in composition yields a spontaneous curvature of the membrane, reshaping the vesicle into a dumbbell which can split. Both pathways are studied using molecular dynamics simulations of the same coarse grained lipid model that has been used before to study spontaneous bilayer and vesicle formation [1], vesicle fusion [2], and vesicle deformations [3]. Using these simulations, the specific conditions to obtain complete fission are investigated for both pathways.