Disruption without disintegration: How are membranes targeted by antimicrobial peptides

Antimicrobial peptides (AMPs) are a class of promising broad-spectrum antibiotics against drug-resistant bacteria. Many of them are found to bind bacterial membranes spontaneously, and cause disruption to membrane integrity by forming membrane pores or increasing membrane permeability, yet more details are needed to understand the delicate interaction under conditions that no pore is present in membranes. The contrast variation technique in neutron scattering affords us to probe the interaction in multi-component fluid model lipid membranes. By taking advantage of the contrast between protiated and deuterated lipids, we have found some AMPs induce a more asymmetric and lateral segregated lipid bilayers with redistribution of charged lipid within intact membranes. For example, Aurein 1.2, a 13-amino acid AMP discovered in Australia frog Litoria genus, drives anionic lipid from the inner leaflet of a bilayer to the outer leaflet. It leads to lateral segregation that is similar to the domain formed below the lipid order−disorder phase-transition temperature. The neutron membrane diffraction results revealed its association mostly with the acyl chain-headgroup region without deep penetration. With neutron spectroscopic techniques such as quasi-elastic neutron scattering and neutron spin echo, we found that Aurein 1.2 restricts the lipid lateral motion in the fluid phase significantly and modifies the elasticity of membranes. With this and our other studies on AMPs such as Alamethicin and melittin, the results point to an alternate mechanism of AMPs on disrupting membrane without disintegrating it. This also provides insights on how cell membranes respond to external stimuli to maintain the integration of the cell boundary. I will discuss how we used neutron scattering to understand more complex membrane systems and the implication for many research on membrane-active molecules.