Diffusion-limited growth of an array of lipid droplets attached to an endoplasmic reticulum

Lipid droplets (LDs) are dynamic organelles that emerge from the endoplasmic reticulum (ER) by accumulation of neutral lipids, such as triacylglycerols (TGs). LDs play an important role in lipid metabolism and in protecting cells from lipotoxicity. LD growth is regulated by a complex interplay of biochemical synthesis, interfacial mechanics, and transport processes. Although molecular pathways governing LD biogenesis have been extensively studied,the physical mechanisms underlying TG accumulation and droplet expansion remain poorly characterized. We developed a finite element model to study diffusion-limited LD growth in a two-dimensional ER membrane with nearly spherical lipid droplets connected to it. Simulations identify the conditions when LD growth is constrained by TG supply. Neighboring droplets compete for TGs, forming depletion zones that drive size disparities and inhibit growth. Our findings reveal biophysical constraints on LD development, including the role of spatial competition in organelle organization.