Regulation of Lipid Droplet Formation by Membrane Tension

Abstract

Cells store excess energy in the form of neutral lipids that are synthesized within the intermonolayer space of the endoplasmic reticulum bilayer. At a certain concentration, the lipids demix from the bilayer to form droplets, which surprisingly mainly bud off toward the cytosol. These droplets are called lipid droplets (LDs) and represent dynamic organelles that play key roles in cellular energy metabolism and homeostasis. How exactly LDs form or bud off from the bilayer is still a not well-understood question for which membrane biophysics can bring good insights. We reconstituted LD formation topology by using two complementary methods: a droplet interface bilayer method, which allows to easily prospect the role of membrane physical chemistry, and giant vesicles embedded with artificial LDs, which enable to prospects the effect of membrane physical properties. These approaches enabled us to decipher that LD budding is controlled by membrane physical chemistry with respect to the physics of three-phase wetting systems, i.e. dictated by the equilibrium of surface tensions. Indeed, the equilibrium between the tension of the bilayer membrane and the tension of the two monolayers enclosing a forming LD determine the budding shape of the latter. Based on the physics of wetting, we identified that an asymmetry in monolayer tensions is an important parameter that controls LD budding side. Our results thus offer new insights on the how proteins might regulate LD formation by dynamically controlling surface tensions.