A broad-spectrum antibacterial hydrogel based on the synergistic action of Fmoc-phenylalanine and Fmoc-lysine in a co-assembled state

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-08, Vol.12 (34), p.8444-8453
• Main Authors: Das Gupta, Bodhisattwa, Halder, Arpita, Vijayakanth, Thangavel, Ghosh, Nandita, Konar, Ranik, Mukherjee, Oindrilla, Gazit, Ehud, Mondal, Sudipta
• Format: Article
• Language: English
• Subjects: Amino acids; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Biomaterials; Biomedical materials; Cell death; Escherichia coli - drug effects; Fluorenes - chemistry; Fluorenes - pharmacology; Hydrogels; Hydrogels - chemical synthesis; Hydrogels - chemistry; Hydrogels - pharmacology; Lysine; Lysine - chemistry; Membranes; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Peptides; Phenylalanine; Phenylalanine - analogs & derivatives; Phenylalanine - chemistry; Phenylalanine - pharmacology; Self-assembly; Staphylococcus aureus - drug effects
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb00948g

Multicomponent biomolecular self-assembly is fundamental for accomplishing complex functionalities of biosystems. Self-assembling peptides, amino acids, and their conjugates serve as a versatile platform for developing biomaterials. However, the co-assembly of multiple building blocks showing synergistic interplay between individual components and producing biomaterials with emergent functional attributes is much less explored. In this study, we have formulated minimalistic co-assembled hydrogels composed of Fmoc-phenylalanine and Fmoc-lysine. The co-assembled systems display broad-spectrum antimicrobial potency, a feature absent in individual building blocks. A comprehensive biophysical analysis demonstrates the physicochemical features of the hydrogels eliciting the antibacterial response. MD simulation further reveals a unique fibrillar architecture with Fmoc-phenylalanine forming the fibril core surrounded by positively charged Fmoc-lysine surface residues, thereby enhancing the interaction with negatively charged bacterial membranes, causing membrane disruption and cell death. Thus, this study provides molecular-level insight into the emergent properties of a multicomponent system, affording an excellent paradigm for developing novel biomaterials. The emergence of a broad-spectrum antibacterial hydrogel by the co-assembly of minimalistic amino acid-based building blocks affords a novel class of biomaterials.