Figure 3.

Hypothetical pathway of biological fusion powered by protein-generated membrane stresses. (a) In the initial state, apposing membrane bilayers are separated by at least a 10–20 nm gap. The contact might involve protein fusogens themselves or be mediated by specialized tethering molecules (green shapes). (b) Fusion proteins induce local bending of membrane bilayer(s) and establish very close contact between the membranes. Generation of large membrane curvature might involve shallow insertion of amphiphilic protein domains (red shapes) into the membrane¹⁰,⁶². The highly stressed and protein-depleted tops of the bilayer bulges are primed for hemifusion and pore opening¹⁰,²⁹,⁵⁶,⁵⁷. (c) Activated fusion proteins (blue shapes) might drive fusion pore expansion by assembling into an interconnected protein coat surrounding the fusion site¹¹⁹. This membrane-associated fusion coat has an intrinsic curvature opposite to that of the budding and fission coats. The coat, bending toward its preferred curvature, deforms the underlying membrane and produces tension that drives fusion and expands the fusion pore.