The Mechanism of Membrane Permeabilization by Peptides: Still an Enigma

Peptide-induced permeabilization of lipid vesicles has been measured for decades and has provided many insights into the sequence-structure-function relationships of membrane-active peptides. However, researchers in the field have noted that many experiments show transient permeabilization, in which a burst of leakage occurs immediately after peptide addition, followed by a slow-down or cessation of leakage before all contents have been released. This widely observed, but rarely studied, phenomenon is not explained by standard equilibrium pore models that are commonly invoked in both experimental and computational studies. Here, we discuss observations of transient permeabilization, and we outline a pathway towards understanding this enigmatic phenomenon.