Electrostatic Interactions between Antimicrobial Peptides and Anionic Membranes: Insights from an Implicit Membrane Model

Abstract

Electrostatic interactions between antimicrobial peptides (AMPs) and anionic bacterial plasma membranes are crucial for their activity and selectivity. In previous implicit models of anionic membranes, the effects of dipole potential and the presence of pores were not included. In this work, we studied the electrostatic interactions of AMPs with the anionic lipids using a membrane model where double layers of charges are used to represent the head group dipole. The electrostatic interactions between AMPs and the anionic membranes and their influence on pore formation are discussed considering the contributions from the dipole potential and the surface potential. We found that the dipole potential had a strong effect on peptide binding and insertion: their location and orientation changed as a function of the strength and the sign of dipole potential. The surface potential, which is caused by the excess charge of anionic lipids however, has influence only on binding. Alamethicin, which is known to form barrel-stave pores, favors binding to cylindrical shaped pores. Melittin and magainin, on the other hand, strongly favors binding to parabola shaped pores, in agreement with the experiments. For these two peptides, increased anionic lipid content enhances this trend while increased dipole potential has the reverse effect.