Bulging and budding of lipid droplets from symmetric and asymmetric membranes: competition between membrane elastic energy and interfacial energy

Abstract

Lipid droplets are ubiquitous intracellular organelles regulating the storage and hydrolysis of neutral lipids, and play key roles in cellular metabolism and other functions such as protein trafficking and coordinating with immune responses. Though lipid droplets are widely observed in eukaryotic organisms, it remains unclear how and what aspects of mechanical interaction between the neutral lipids and lipid membranes contribute to the bulging and budding of nascent lipid droplets from the endoplasmic reticulum, and particularly effects of membrane asymmetry and spontaneous curvature on lipid droplet formation are not theoretically rationalized. Here we conduct a comprehensive theoretical study on the mechanical behaviors of lipid droplets embedded in between two lipid monolayers of the same or different mechanical properties, and indicate that the membrane bending rigidity, tension and spontaneous curvature, lipid droplet size, and interfacial energy between the neutral lipids and covering lipid leaflets collectively play key roles in regulating the growth and budding transition of lipid droplets. It is found that the embedded neutral lipids beyond a critical volume could undergo a discontinuous shape transition from a lens-like configuration to a budding state with a spherical bulge configuration. Moreover, a positive lipid monolayer spontaneous curvature and smaller monolayer bending rigidity and tension facilitate the budding transition. Budding phase diagrams accounting for these characteristic interaction states are established. Based on the membrane theory at small deformation before budding and the assumption of spherical configuration after budding, we obtain analytical solutions on the bulge profiles, which can be used to estimate the value of interfacial energy. Our results uncover the fundamental mechanics of the lipid droplet formation and budding, and are of broad interest to the studies of echogenic liposome stability and cellular incorporation of nanoparticles.