Direct Observation of Gram Negative Bacterial Membrane Disruption by Supramolecular Antimicrobials

Cyclic peptides with alternating side chain stereochemistry are capable of self-assembling into long nanotubes. The conjugation of polymers to these peptides renders the resulting nanotubes water soluble, whilst providing functionality. In response to the rising global threat of increasing antimicrobial resistance, we have been developing cationic cyclic peptide-polymer conjugates to target anionic Gram-negative bacterial membranes as supramolecular antimicrobials. Here, we propose to assemble asymmetric planar floating lipid bilayers on functionalised gold surfaces to mimic the outer membrane of Gram-negative bacteria. By using neutron reflectometry and exploiting isotopic contrast, we aim to determine the mechanism of membrane disruption by these materials whilst obtaining information relating the molecular properties of cyclic peptide-polymer conjugates to their antimicrobial activity