Figure 7. Energy landscape of sterol-mediated membrane bending during clathrin-mediated endocytosis.
Cholesterol abundance and sterol identity strongly influence the energetics of membrane bending at multiple stages of clathrin-coated vesicle formation, facilitating curvature initiation and formation of the highly curved vesicle neck. Proposed mechanisms of sterol dynamics during membrane remodeling include cholesterol interleaflet flip-flop, which may relieve compression and expansion of the PM leaflets to negate energy costs associated with PM deformation and tight lipid packing of sterols, which are thought to underlie the formation of Lo and Ld domains (e.g., lipid rafts) to support membrane budding, as increasing curvature minimizes line tension between phase boundaries. The multifaceted properties of sterols likely reduce the energetic requirements necessary for membrane remodeling during clathrin-mediated endocytosis.