Designing imidazole capped laminin inspired peptide hydrogels in the presence of biologically relevant metal salts to fabricate advanced biofunctional scaffold for controlling cellular behaviour

Abstract

Self-assembling peptides inspired from extracellular matrix (ECM) proteins provide a versatile platform for tissue engineering due to their biocompatible and biodegradable nature. Short oligopeptides can self-assemble into supramolecular hydrogels with nanofibrillar architecture supporting cellular adhesion and proliferation. Herein, we design a novel laminin-inspired peptide, Imidazole-Phe-Ser-Ile-Lys-Val-Ala-Val (Imi-FSIKVAV), which demonstrates the ability to self-assemble into nanofibers at physiological pH, aiming to improve hydrophilicity and biocompatibility. The incorporation of imidazole, a common motif in biomolecules like histidine, introduces binding sites for metal ion coordination. Our findings indicate that the addition of biologically relevant metal ions such as Ca²⁺ or Mg²⁺ significantly improves the self-assembling propensity, resulting in the formation of dense nanostructured hydrogel. These metal-ion coordinated hydrogels exhibit superior mechanical properties and support the cellular adhesion and proliferation of neuroblastoma cells. By leveraging the unique interactions between peptides and metal ions, we can create advanced materials that can not only mimic the structural characteristics of the natural ECM but can also promote cellular functions necessary for tissue repair and regeneration. Our research highlights the potential of metal-ion-mediated peptide self-assembly as a strategy for designing innovative biomaterials suitable for diverse biomedical applications, paving the way for future advancements in tissue engineering and regenerative therapies.