In this work, we focus on elastic and structural interactions of two novel engineered cationic antimicrobial peptides (eCAPs) each with four bacterial lipid membrane mimics.  The linear eCAPs are WLBU2 and D8, each composed of 3 types of amino acids (tryptophan, arginine and valine) with a total length of 24 residues. In D8, all valines (8 in total) are the D-enantiomer. Both eCAPs demonstrate broad-spectrum antimicrobial activity and efficiently kill  both gram-negative and gram-positive bacteria. Bending moduli, lipid chain order and membrane structure are obtained using x-ray diffuse scattering (XDS) and the position of each peptide in the membrane is determined with neutron reflectivity (NR).  We previously showed using CD and NMR that WLBU2 is primarily alpha-helical, while D8 is primarily random coil in membranes, which indicated that eCAP secondary structure is not a critical factor for bacterial killing, consistent with the diversity in secondary structures observed in natural antimicrobial peptides. However, membrane thinning and the dual location of both WLBU2 and D8 in the headgroup and in the hydrocarbon regions may lead to the membrane destabilization that causes killing of both gram-negative and -positive bacteria. Our published elastic results showed that both WLBU2 and D8 exhibit irregular, non- monotonic changes in bending moduli as a function of increasing concentration of peptide. We suggested that domains with different material moduli are juxtaposed, leading to unstable domain walls. It is possible that each peptide aligns within the domain walls in the hydrocarbon region of gram-negative and -positive bacteria. While neither peptide thins the gram-negative lipopolysaccharide outer membrane model, they both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm.<br/> <br/><br/>

Elastic and structural interactions of eCAPs WLBU2 and D8 with bacterial lipid membrane mimics

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.