Materials derived from the human elastin-like polypeptide fusion with an antimicrobial peptide strongly promote cell adhesion

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2024-09, Vol.12 (36), p.8966-8976
• Main Authors: Colomina-Alfaro, Laura, Sist, Paola, D'Andrea, Paola, Urbani, Ranieri, Marchesan, Silvia, Stamboulis, Artemis, Bandiera, Antonella
• Format: Article
• Language: English
• Subjects: Activity recognition; Adhesion; Adhesive strength; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial peptides; Antimicrobial Peptides - chemistry; Antimicrobial Peptides - pharmacology; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Biodegradability; Biodegradation; Biological activity; Biological effects; Biomimetic materials; Biomimetics; Biopolymers; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell fusion; Defensins; E coli; Elastin; Elastin - chemistry; Elastin - pharmacology; Elastin-Like Polypeptides; Escherichia coli - drug effects; Fusion protein; Gene fusion; Humans; Microbial Sensitivity Tests; Multitasking; Peptides; Peptides - chemistry; Peptides - pharmacology; Polypeptides; Sustainable production
• ISSN: 2050-750X; 2050-7518; 2050-7518
• DOI: 10.1039/d4tb00319e

Protein and peptide materials have attracted great interest in recent years, especially for biological applications, in light of their possibility to easily encode bioactivity whilst maintaining cytocompatibility and biodegradability. Heterologous recombinant expression to produce antimicrobial peptides is increasingly considered a convenient alternative for the transition from conventional methods to more sustainable production systems. The human elastin-like polypeptide (HELP) has proven to be a valuable fusion carrier, and due to its cutting-edge properties, biomimetic materials with antimicrobial capacity have been successfully developed. In this work, we have taken advantage of this platform to produce a difficult-to-synthesise sequence as that of the human β-defensin 1 (hBD1), an amphipathic cationic peptide with structural folding constraints relevant to its bioactivity. In the design of the gene, highly specific endoproteinases recognition sites were introduced to release the active forms of hBD1. After the expression and purification of the new fusion construct, its biological activity was evaluated. It was found that both the fusion biopolymer and the released active forms can inhibit the growth of Escherichia coli in redox environments. Remarkably, 2D and 3D materials derived from the biopolymer showed a strong cell adhesion-promoting activity. These results suggest that HELP represents a multitasking platform that not only facilitates the production of bioactive domains and derived materials but could also pave the way for the development of new approaches to study biological interactions at the molecular level. An elastin-like fusion of the difficult-to-synthesise human β-defensin 1 domain was produced retaining the antimicrobial properties of the peptide. The new biopolymer was used to produce coatings and hydrogel-like matrices that promoted cell adhesion.