Various physicochemical properties play important roles in the membrane activities of amphipathic antimicrobial peptides. To examine the effects of the polar angle, two model peptides, θp100 and θp180, with polar angles of 100° and 180°, respectively, were designed, and their interactions with membranes were investigated in detail. These peptides have almost identical physicochemical properties except for polar angle. Like naturally occurring peptides, these peptides selectively bind to acidic membranes, assuming amphipathic α-helices, and formed peptide-lipid supramolecular complex pores accompanied by lipid flip-flop and peptide translocation. Despite its somewhat lower membrane affinity, θp100 exhibited higher membrane permeabilization activity, a greater flip-flop rate, as well as more antimicrobial activity due to a higher pore formation rate compared with θp180. Consistent with these results, the peptide translocation rate of θp100 was higher. Furthermore, the number of peptides constituting θp100 pores was less than that of θp180, and θp100 pores involved more lipid molecules, as reflected by its cation selectivity. The polar angle was found to be an important parameter determining peptide-lipid interactions.
