Lipid Demixing Reduces Energy Barriers for High Curvature Vesicle Budding

Budding relies on membrane asymmetry, including composition, area, and osmotic differences, and involves large curvature changes in nanoscale lipid vesicles. So far, the combined impact of asymmetry and high curvatures on budding has remained unknown. Here, using continuum elastic theory, the budding pathway is detailed under realistic conditions. It shows that budding is less favored in smaller vesicles but lipid demixing can significantly reduce its energy barrier and yet high compositional deviations of more than 7% between the bud and vesicle only occur with phase separation on the bud.