Bioinspired Genetic and Chemical Engineering of Protein Hydrogels for Programable Multi‐Responsive Actuation

Protein hydrogels with tailored stimuli-responsive features and tunable stiffness have garnered considerable attention due to the growing demand for biomedical soft robotics. However, integrating multiple responsive features toward intelligent yet biocompatible actuators remains challenging. Here, a facile approach that synergistically combines genetic and chemical engineering for the design of protein hydrogel actuators with programmable complex spatial deformation is reported. Genetically engineered silk-elastin-like proteins (SELPs) are encoded with stimuli-responsive motifs and enzymatic crosslinking sites via simulation-guided genetic engineering strategies. Chemical modifications of the recombinant proteins are also used as secondary control points to tailor material properties, responsive features, and anisotropy in SELP hydrogels. As a proof-of-concept example, diazonium coupling chemistry is exploited to incorporate sulfanilic acid groups onto the tyrosine residues in the elastin domains of SELPs to achieve patterned SELP hydrogels. These hydrogels can be programmed to perform various actuations, including controllable bending, buckling, and complex deformation under external stimuli, such as temperature, ionic strength, or pH. With the inspiration of genetic and chemical engineering in natural organisms, this work offers a predictable, tunable, and environmentally sustainable approach for the fabrication of programmed intelligent soft actuators, with implications for a variety of biomedical materials and biorobotics needs.