A mechanistic investigation of cell-penetrating Tat peptides with supported lipid membranes

► Tat peptides disrupt bacterial-mimetic membranes via surface-active mechanisms. ► Peptide binding increases with greater negatively charged lipid composition. ► Membrane disruption decreases with increasing negative membrane charge. ► Membrane disruption less for Tat (44-57) compared with Tat (49-57). ► Both Tat peptides bind to mammalian-mimetic membranes without disruption.