Vesicle deformation and division induced by flip-flops of lipid molecules

We investigated the deformation of small unilamellar vesicles (SUVs) induced by flip-flops of lipids using coarse-grained molecular dynamics simulations. In the case of single-component SUVs composed of zero spontaneous curvature lipids (ZLs), the flip-flop of ZLs deformed stomatocyte-shaped SUVs into an oblate shape, whereas pear-shaped SUVs were deformed into a prolate shape. These two equilibrium shapes comply with the local minima of elastic energy. In the case of binary vesicles composed of ZLs and negative spontaneous curvature lipids (NLs), the vesicle deformation pathway depended on the initial NL distribution in the bilayer. If the initial difference in the NL concentration between the outer and inner leaflets was small, the flip-flop of ZLs and NLs rapidly deformed pear-shaped SUVs into an equilibrium prolate shape. On the other hand, when NLs were localised in the inner leaflet, the flip-flop of ZLs and NLs deformed pear-shaped SUVs into a limiting shape and then induced vesicle division. Because the flip-flop rate of NLs is much faster than that of ZLs, the total free energy was first relaxed by the flip-flop of NLs and then by that of ZLs. This kinetic effect is responsible for the observed vesicle division induced by flip-flops.