Mechanical
perturbations are ubiquitous in living cells, and many
biological functions are dependent on the mechanical response of lipid
membranes. Recent force-spectroscopy studies have captured the stepwise
fracture of stacks of bilayers, avoiding substrate effects. However,
the effect of stacking bilayers, as well as the exact molecular mechanism
of the fracture process, is unknown. Here, we use atomistic and coarse-grained
force-clamp molecular dynamics simulation to assess the effects of
mechanical indentation on stacked and single bilayers. Our simulations
show that the rupture process obeys the laws of force-activated barrier
crossing, and stacking multiple membranes stabilizes them. The rupture
times follow a log-normal distribution which allows the interpretation
of membrane rupture as a pore-growth process. Indenter hydrophobicity
determines the type of pore formation, the preferred dwelling region,
and the resistance of the bilayer against rupture. Our results provide
a better understanding of the nanomechanics underlying the plastic
rupture of lipid membranes.