Area difference between monolayers facilitates budding of lipid droplets from vesicles

Lipid droplets (LDs) are intracellular organelles that play a central role in cellular lipid balance and energy homeostasis. Though extensive experimental studies have been carried out on LD biogenesis, relatively little is known about the mechanical interaction between LDs and vesicles, and in particular effects of area difference between vesicle leaflets on LD evolution are not theoretically rationalized. Here we theoretically explore how the monolayer area difference regulates the budding and morphological evolution of an LD embedded in the vesicle membrane. It is shown that both the monolayer area difference and interfacial energy strength, attributed to the LD-membrane contact, facilitate the LD budding with the confined LD evolving from a bulge to a spherical protrusion. The budding direction is towards the monolayer with more phospholipids. Outward and inward budding phase diagrams are established with respect to the interfacial energy strength and area ratio between the outer and inner monolayers. Moreover, the osmotic pressure of the vesicle promotes the LD budding at a small monolayer area difference and inhibits the budding at a relatively large monolayer area difference.