Dependence of Antimicrobial Selectivity and Potency on Oligomer Structure Investigated Using Substrate Supported Lipid Bilayers and Sum Frequency Generation Vibrational Spectroscopy

Abstract

Sum frequency generation (SFG) vibrational spectroscopy was used to study interactions between solid-supported lipid bilayers mimicking microbial and erythrocyte cellular membranes and synthetic antimicrobial arylamide oligomers named 2, 3, and 4, designed with the facial amphiphilicity common to naturally occurring antimicrobial peptides. The three compounds have the same backbone structure but varied side chains. The inherent interfacial sensitivity of SFG allowed for simultaneous monitoring of lipid ordering in the individual bilayer leaflets and orientation of 2, 3, and 4 upon interaction with the bilayer. Critical concentrations at which the inner leaflet is disrupted were determined for each oligomer. Spectral evidence of the oligomers' interaction with the bilayer below the critical concentrations was also found. Oligomers 2 and 3 tilted toward the bilayer surface normal, in agreement with previous experimental and simulation results. These oligomers selectively interact with microbial membrane models over erythrocyte membrane models, correlating well to previously published SFG studies on antimicrobial oligomer 1. It was shown that the oligomers interact with the lipid bilayers differently, indicating their different activity and selectivity. This research further shows that SFG is a particularly useful technique for the investigation of interaction mechanisms between cell membranes and membrane-active molecules. Additionally, SFG provides details of the specific interactions between these novel antimicrobials and lipid bilayers.