Rational design of water-soluble, homotypic keratins self-assembly with enhanced bioactivities

Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications. Herein, we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code. In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins. Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment, without urea and after QTY modification. Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins. Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly, hemostasis, and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.