Determining the Effects of Membrane-Interacting Peptides on Membrane Integrity

In the study of cell-penetrating and membrane-translocating peptides, a fundamental question occurs as to the contribution arising from fundamental peptide-membrane interactions, relative to the contribution arising from the biology and energy of the cell, mostly occurring in the form of endocytosis and subsequent events. A commonly used approach to begin addressing these mechanistic questions is to measure the degree to which peptides can interact with, and physically disrupt, the integrity of synthetic lipid bilayers. Here, we describe a set of experimental methods that can be used to measure the potency, kinetics, transience, and the effective size of peptide-induced membrane disruption.