Nucleation free energy of pore formation in an amphiphilic bilayer studied by molecular dynamics simulations

Abstract

The formation of a pore in a membrane requires a considerable rearrangement of the amphiphilic molecules about to form the bilayer edge surrounding the pore, and hence is accompanied by a steep increase of the free energy. Recent rupture and conductance experiments suggest that this reshuffling process is also responsible for a small energy barrier that stabilizes "prepores" with diameters of less than 1 nm, rendering both the opening and closing of pores an activated process. We use the potential of mean constraint force method to study this free energy profile, as a function of pore radius, in a coarse grained bilayer model. The calculations show that the free energy rises by (15-20) kT during pore opening, making it an extremely rare nucleation event. Although we do not observe a barrier to pore closure, the results do make the existence of such a barrier plausible. For larger pores we find a smooth transition to Litster's model, from which a line tension coefficient of about 3.7 x 10(-11) J m(-1) is deduced.