From the expanded fusion pore at metastable equilibrium (ξ e ∼ 0.4) it is observed that the cost to further expand it to its maximum radius at ξ e ∼ 0.75 is reduced by one and two Syt1-C2B domains by ∼ 20kJ/mol each, taking the membranes-only system as reference (black line). Therefore, in agreement with experimental observations, 8,65-67 the presence of Syt1-C2B domains facilitates the metastable fusion pore to evolve towards expansion.