Figure 7.

Model of promotion of SNARE-mediated fusion by cholesterol. Cholesterol (triangles) clusters t-SNAREs in target membranes (left), increasing vesicle docking rates and providing multiple t-SNAREs that are instantly available for accelerated fusion (right). Once initiated, the openness of the flickering pore is increased by cholesterol 1) directly, by lowering the bending energy of the pore (Fig. S5), whose negative curvature is compatible with cholesterol’s large, negative spontaneous curvature, ∼−0.4 ${\text{nm}}^{-1}$ (55) (blow up, right); or 2) indirectly, by increasing the number of SNAREpins at the fusion pore. Increased openness stabilizes the pore and may increase content release rates and accelerate pore dilation (Fig. 1). To see this figure in color, go online.