A non-covalent binding strategy for the stabilization of fish collagen triple helices to promote its applications

Collagen, with its most characteristic structural unit, the triple helix, has wide applications in pharmaceutical and cosmetic industries. However, the application of collagen is limited by its poor thermal stability, especially fish collagen. Fish collagen, despite its abundance and eco-friendly sourcing, faces challenges like low melting temperatures and mechanical fragility due to its distinct composition. In this study, the focus was on exploring strategies to enhance the stability of fish collagen for potential human applications. To address this, our research investigated a non-covalent binding strategy, by using heat shock protein 47 (Hsp47) from zebrafish and human to stabilize fish collagen. The co-application of Hsp47 dramatically improved the rates of folding and markedly increased the denaturation temperature of fish collagen from 31.7 °C to 37.7 °C, demonstrating promising outcomes for potential in vitro applications. Optical Nanoscopy Electron Microscopy (OpNS-EM) imaging demonstrates the complex formation between Hsp47 and collagen fibers, shedding light on their interaction dynamics, while cytotoxicity assays affirm the safety of the Collagen-Hsp47 complex on human keratinocytes. This pioneering methodology applies a viable approach to stabilize fish collagen, expanding its potential applications across human-related domains.