Interaction between a Cationic Surfactant-like Peptide and Lipid Vesicles and Its Relationship to Antimicrobial Activity

Ashkan Dehsorkhi,Valeria Castelletto,Ian W Hamley,Jani Seitsonen,Janne Ruokolainen

doi:10.1021/la403447u

Abstract

We investigate the properties of an antimicrobial surfactant-like peptide (Ala)6(Arg), A6R, containing a cationic headgroup. The interaction of this peptide with zwitterionic (DPPC) lipid vesicles is investigated using a range of microscopic, X-ray scattering, spectroscopic, and calorimetric methods. The β-sheet structure adopted by A6R is disrupted in the presence of DPPC. A strong effect on the small-angle X-ray scattering profile is observed: the Bragg peaks from the DPPC bilayers in the vesicle walls are eliminated in the presence of A6R and only bilayer form factor peaks are observed. All of these observations point to the interaction of A6R with DPPC bilayers. These studies provide insight into interactions between a model cationic peptide and vesicles, relevant to understanding the action of antimicrobial peptides on lipid membranes. Notably, peptide A6R exhibits antimicrobial activity without membrane lysis.

Highlights

Surfactant-like peptides (SLPs) have a remarkable ability to self-assemble into different nanostructures, primarily due to their amphiphilic nature
At the higher peptide concentration, the reduction is greater for S. aureus than for E. coli (data shown in Supporting Information (SI) Figure 1a)
A6R interacts with DPPC vesicles leading to changes in the vesicle wall layer spacing such that the Small-Angle and X-ray Scattering (SAXS) structure factor peaks present for DPPC vesicles are eliminated and only the form factor of isolated bilayers is observed

Summary

■ INTRODUCTION

Surfactant-like peptides (SLPs) have a remarkable ability to self-assemble into different nanostructures, primarily due to their amphiphilic nature. Solutions of 0.5, 1, and 2 wt % DPPC vesicles were first prepared followed by the addition of 1 wt %. The grids with vitrified sample solution were maintained at liquid nitrogen temperature and cryo-transferred to the microscope. Measurements were performed on stalks prepared by drying filaments of solutions containing 1 wt % A6R mixed with 0.5, 1, and 2 wt % DPPC. CD was performed on solution mixtures containing DPPC vesicles with A6R added later, with a 0.5 nm step, 1 nm bandwidth and 1 s collection time per step at 20 °C. The ITC experiment was programmed to run 20 injections of 2 μL volume of the titrant solution (1 wt % A6R) into the working cell (0.1 wt % DPPC) with 300 s lag between each injection to ensure return to the baseline. The data was analyzed using Origin 7 (MicroCal) by fitting the curve using the one set of sites model

■ RESULTS

■ SUMMARY AND DISCUSSION

■ REFERENCES