While it is clear that neither LL-37 nor indolicidin are forming transmembrane and multipeptide structural pores, and that all peptides facilitate millisecond scale equilibration across the membrane, the rapid ion transport is perhaps most surprising in the case of indolicidin. Hence, indolicidin was chosen for further consideration with molecular dynamics simulations. Closer inspection of our previous MD simulations revealed the passage of ions through a transient water pore formed due to indolicidin induced lipid flipping. The diffusion coefficient D for the ions through the membrane obtained from the MD was used in a diffusional model to explain the experimental discharge kinetics. Interestingly, it was not possible to fit the experimental data using a conventional diffusion model, assuming a fixed average number of pores present in the vesicle. In fact, lipid-flipping, which induces pore formation, is associated with peristaltic motion of the membrane-bound peptide (Figure , and ref. ). In the presence of an osmotic gradient acting in the direction of this motion, we thus adopted a diffusional model where the average number of pores decreases according to the decay of the osmotic pressure Π(t) = ∆c(t)k b T (see SI).