Fabrication of cytocompatible self-assembling antimicrobial nanofibers via peptide self-assembly

Statement of Purpose: Bacterial resistance to conventional antibiotics has become a major threat to public health and ~$20 billion in direct medical costs are associated with treatment of antibiotic-resistant infections in the US each year.^1,2 Antimicrobial peptides (AMPs) are considered promising alternatives to conventional antibiotics, however, their widespread use and translation into clinical application is hampered by several intrinsic limitations, including their susceptibility to proteases and severe toxicity towards host cells.³ To enhance AMP-based antimicrobial materials design and potentially overcome the drawbacks of traditional AMPs, we recently developed a family of cytocompatible self-assembling antimicrobial nanofibers (SAANs) based on the supramolecular assembly of de novo designed multidomain peptides (MDPs).^4-5 Our central hypothesis is that self-assembly is the key to SAANs’ improved cytocompability and bacterial cell selectivity. Unlike most conventional AMPs that exist as monomers in solution, MDPs can form supramolecular b-sheet nanofibers in which the hydrophobic residues and non-polar surface are partially masked between the two sheets, which has been proven as an important factor to minimize the cytotoxicity of MDPs toward mammalian cells. In this work, we will validate the self-assembling platform which can be potentially used for the re-engineering or ‘re-formatting’ of thousands of natural and synthetic AMPs, thus greatly boosting their therapeutic potential.