Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity

• DOI: 10.1038/s41467-017-01447-x
• Publication Date: 2017-11-03T03:00:24Z
• Authors: Lee Schnaider; Sayanti Brahmachari; Nathan W. Schmidt; Bruk Mensa; Shira Shaham-Niv; Darya Bychenko; Lihi Adler-Abramo...; Linda J. W. Shimon; Sofiya Kolusheva; William F. DeGrado; Ehud Gazit
• Keywords: 0301 basic medicine; Physiological; Science; Phenylalanine; Biomedical Engineering; 610; Bioengineering; Microbial Sensitivity Tests; Stress; Electron; Article; Macromolecular and Materials Chemistry; 03 medical and health sciences; Engineering; Anti-Infective Agents; Stress, Physiological; Escherichia coli; Nanotechnology; Humans; Scanning; Microscopy; Tissue Scaffolds; Glycylglycine; Circular Dichroism; Q; Cell Membrane; Bacterial; Dipeptides; Gene Expression Regulation, Bacterial; 620; Nanostructures; HEK293 Cells; Gene Expression Regulation; Chemical Sciences; Microscopy, Electron, Scanning; Biotechnology

AbstractPeptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials.