On the Minimum Energy Path to Membrane Pore Formation

Several experimental methods have been developed to study the mechanical response of vesicles under an applied tension. Of particular note are the micropipette aspiration techniques and the use of a viscous solution to extend the lifetime of pores. MD simulations have also been used to study the energetic and structural properties of these transient pores on a molecular level. However, they often require extremely high tensions beyond the regime where pore formation is a thermally-activated event. We approach the nucleation problem by combining the string method with dynamic self-consistent field (DSCF) theory to obtain the full minimum energy path (MEP) to pore formation for a range of surface tensions $\gamma$. We compare our results with classical nucleation theory (CNT). Near the coexistence ($\gamma \rightarrow 0$) the rim of the pore is well-defined and the line tension is well approximated by the macroscopic definition given by CNT. However, when the free energy barrier is within $\sim 10~\rm kT$, the transition state is somewhere between a stalk-like structure and a thinned membrane leading to a hole that is partially exposed to solvents. These molecular rearrangements involved in the formation of a pore are not captured by CNT.