Fabrication and Microscopic and Spectroscopic Characterization of Cytocompatible Self-Assembling Antimicrobial Nanofibers

The discovery of antimicrobial peptides (AMPs) has brought tremendous promise and opportunities to overcome the prevalence of bacterial resistance to commonly used antibiotics. However, their widespread use and translation into clinical application is hampered by the moderate to severe hemolytic activity and cytotoxicity. Here, we presented and validated a supramolecular platform for the construction of hemo- and cytocompatible AMP-based nanomaterials, termed self-assembling antimicrobial nanofibers (SAANs). SAANs, the “nucleus” of our antimicrobial therapeutic platform, are supramolecular assemblies of de novo designed AMPs that undergo programmed self-assembly into nanostructured fibers to “punch holes” in the bacterial membrane, thus killing the bacterial pathogen. In this study, we performed solid-state NMR spectroscopy showing predominant antiparallel β-sheet assemblies rather than monomers to interact with liposomes. We investigated the mode of antimicrobial action of SAANs using transmission electr...