Reversible light-responsive protein hydrogel for on-demand cell encapsulation and release.

The design of biomaterials that can reconfigure on-demand in response to external stimuli is an emerging area in materials research. However, achieving reversible assembly of protein-based biomaterials by light input remains a major challenge. Here, we present the engineering of a new protein material that is capable of switching between liquid and solid state reversibly, controlled by lights of different wavelengths. The materials are created by incorporating a light-responsive mutant Dronpa protein domain into the backbone of Elastin-Like Proteins (termed DELPs). We show that the DELP material can respond to light and undergo multiple cycles of switching between hydrogel and solution, outperforming the conventional irreversible materials. Additionally, the material is biocompatible with long-term cell proliferation in both adherent and suspension cells. Building on the reversible assembly of the material, we demonstrate efficient cell encapsulation and release upon light triggers. The design principle of incorporating a light-responsive protein element into a structural protein matrix, as demonstrated in this work enables, a broad range of other applications that require adaptive materials to intelligently interface with dynamic biological systems and environments. STATEMENT OF SIGNIFICANCE: This work generates a new class of "smart" biomaterials that uniquely switches between liquid and gel states in response to light input. Light input can be precisely delivered in space and time, highly tunable through wavelengths, intensities, and durations of light exposure. In prior research, light-responsive biomaterials are mostly irreversible, limiting their use to only uni-directional applications and the materials cannot be re-used. In contrast, this material robustly displays reversible switching between liquid and gel using a light-responsive crosslinker. Furthermore, the material is biocompatible, programmable, and suitable for broad applications including but not limited to cell encapsulation, controlled release, tissue engineering, and cell/tissue mechanobiology.