N-Acylation of Antimicrobial Peptides Causes Different Mode of Cell Membrane Damage

Abstract

spectroscopy on lipid bilayer stacks with TAT 'd-functionalized' probes to monitor both the TAT position within a single bilayer and the associated force with microsecond resolution. To our knowledge these results present the first direct quantification of the mechanics of TAT penetration and the first demonstration that the different regimes identified in dynamic force spectroscopy correspond to distinct mechanisms. The AFM results show that TAT by itself does indeed alter the membrane structure. Additional results from lysine oligomer probes indicate that TAT's arginine groups are key to these TAT-lipid interactions, since probes functionalized with a lysine oligomer did not induce bilayer thinning. Though TAT strongly interacts with the lipid bilayer, the energy barrier for TAT penetration is actually 38kT higher than for probes functionalized with 11-mercaptoundecanoic acid. These results corroborate many of the conclusions from molecular dynamics simulations on TAT-lipid systems, which indicate that TAT does not penetrate bilayers directly.