Versatile Engineered Protein Hydrogels Enabling Decoupled Mechanical and Biochemical Tuning for Cell Adhesion and Neurite Growth

Development of engineered protein materials with wide-ranging mechanical strength and stiffness while maintaining the biofunctionality of protein molecules within remains a big challenge. Here we demonstrate the synthesis of protein hydrogels by photochemically cross-linking recombinant mussel foot protein-3 (Mfp3). The hydrogels’ stiffness can be broadly tuned by adjusting the concentration of protein polymers or co-oxidants, or light intensity needed for the chemical cross-linking. The protein polymers were also designed to contain SpyCatcher domains, which enabled postgelation decoration with diverse folded globular proteins under mild physiological conditions. Not only did the resulting hydrogels support the adhesion and proliferation of a variety of cell lines, but they were also able to activate the JAK/STAT3 pathway and induce neurite growth via the covalently immobilized leukemia inhibitory factor (LIF). These results illustrate a new strategy for designing bioactive materials for regenerative neurobiology.