Rational design of water‐soluble, homotypic keratins self‐assembly with enhanced bioactivities
Jie Chen,
Yumei Wang,
Jia Deng,
Rui Qing,
Yaxi Yang,
Xiaoliang Chen,
Zibin Gao,
Bochu Wang,
Shilei Hao
Affiliations
Jie Chen
Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing China
Yumei Wang
Department of Nuclear Medicine Chongqing University Cancer Hospital Chongqing China
Jia Deng
College of Environment and Resources Chongqing Technology and Business University Chongqing China
Rui Qing
State Key Laboratory of Microbial Metabolism School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai China
Yaxi Yang
Department of Genetics College of Biological Science University of California—Davis Davis California USA
Xiaoliang Chen
Department of Nuclear Medicine Chongqing University Cancer Hospital Chongqing China
Zibin Gao
State Key Laboratory Breeding Base Hebei Province Key Laboratory of Molecular Chemistry for Drugs Hebei University of Science and Technology Shijiazhuang China
Bochu Wang
Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing China
Shilei Hao
Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering Chongqing University Chongqing China
Abstract 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.
