This effect is also observable for the system containing one C2B domain, which also pushes the nascent fusion pore towards meta-stabilization (see figure ) and although less significantly, also reduces the cost for expansion for ξ e > 0.4 (see figure ). However, the absence of a clear reduction of the nucleation expansion barrier ΔG ne makes the overall effect less noticeable. Accordingly, collaborative mechanisms between pairs of C2B domains (or the tandem C2A:C2B) have already shown to be key during membrane fusion. In agreement, Cafiso and collaborators hypothesized that Syt1 could mediate the transition during a fusion event by either lowering an energy barrier towards pore expansion (the metastable fusion pore) or by preventing the system from getting trapped at an early intermediate state (a just nucleated fusion pore), as also proposed by Kiessling and collaborators. Moreover, Chapman and collaborators recently observed that the interaction of Syt1 with PIP 2 serves to stabilize opening of fusion pores, while Janshoff and collaborators suggested that Syt1 collaborates to accelerate fusion kinetics in the presence of Ca 2+ .