Biological implications of these results are of major importance. First, C2B domains facilitate the expansion of the fusion pore beyond the metastable state at ξ e ∼ 0.4 (R ef f ∼ 0.5nm). Second, the nucleation-expansion energy barrier that defines the metastability of the first expanded pore at ξ e ∼ 0.4, is significantly reduced by a pair of C2B domains.