Antimicrobial Peptide Impacts the Lateral Diffusion and Bending Rigidity of Phospholipid Membrane

Abstract

Antimicrobial peptides (AMPs) are the first line of defense system against foreign microorganisms. They are well known for their strong interaction with the cell membrane of pathogens. Quasielastic neutron scattering (QENS) and Neutron spin echo (NSE) measurements have been carried out on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) membrane to understand the effect of melittin, an important AMP on the dynamical and mechanical behavior of membrane. Even at low concentration (0.2 mol%), the addition of melittin is found to influence the membrane dynamics significantly in a different way, depending on the phase of the lipid bilayers. In the gel phase, it acts as a plasticizer, enhancing the lateral motion of DMPC. However, in the fluid phase, it acts as a stiffening agent, hindering the lateral motion of the lipid molecules. Various interesting results on the impact of melittin on the phase behavior and lateral diffusion of the membrane will be discussed here. Their importance originate from the fact that many cellular functions, including cell signaling, membrane trafficking, and cell recognition are controlled to a great extent by the lateral diffusion of lipids in the membrane. NSE measurements indicate that incorporation of melittin modify the bending rigidity of the membrane, which is found to decrease with the concentration of melittin. Cholesterol is a vital component of erythrocyte membranes, which is a natural target for melittin. To understand the role of cholesterol, both QENS and NSE experiments have also been carried out on cholesterol-supplemented DMPC membrane in the absence and presence of melittin. Our measurements show that the destabilizing effect of melittin on the membranes can be mitigated by the presence of cholesterol. This study might provide new insights into the mechanism of action of antimicrobial peptides and their selective toxicity towards foreign microorganisms.