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

Om Prakash Narayan; Jiawei Dong; Miao Huang; Liqiang Chen; Lu Liu; Vivian Nguyen; Abdul Vehab Dozic; Xiangping Liu; Huiliang Wang; Qian Yin; Xin Tang; Juan Guan

doi:10.1016/j.actbio.2025.01.012

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

Acta Biomater. 2025 Jan 10:S1742-7061(25)00020-0. doi: 10.1016/j.actbio.2025.01.012. Online ahead of print.

Authors

Om Prakash Narayan¹, Jiawei Dong¹, Miao Huang², Liqiang Chen³, Lu Liu¹, Vivian Nguyen⁴, Abdul Vehab Dozic⁵, Xiangping Liu³, Huiliang Wang³, Qian Yin³, Xin Tang⁶, Juan Guan⁷

Affiliations

¹ Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX, 78712, USA.
² Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA; University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA.
³ Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
⁴ Department of Biology, University of Florida, Gainesville, FL, 32611, USA.
⁵ Department of Physics, University of Florida, Gainesville, FL, 32611, USA.
⁶ Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, 32611, USA; University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610, USA. Electronic address: xin.tang@ufl.edu.
⁷ Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: juanguan@utexas.edu.

PMID: 39800098
DOI: 10.1016/j.actbio.2025.01.012

Abstract

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.

Keywords: Biomaterial; Cell encapsulation; Light responsive proteins; Stimuli responsive proteins.