Engineering dynamic protein-based hydrogels

Hydrogels are water-containing soft materials made of cross-linked polymer networks. Hydrogels can emulate many features of native tissues and organisms, and have therefore found many applications in biomedical studies. Recently, driven by the needs for stimuli-responsive materials in various biomedical applications, “dynamic” hydrogels that can change their physical, chemical, biological, or mechanical properties have attracted increasing interest. Recombinant proteins are promising hydrogel building blocks due to their biocompatibility, diverse biofunctions, and designable structures. Moreover, stimuli-responsive conformational changes and interactions of proteins provide possibilities for constructing dynamic protein-based hydrogels. This thesis reviews the state-of-the-art studies of dynamic protein-based hydrogels, including the cross-linking methods, the design principles, and the future directions of this field. Driven by the needs for more predictable, sensitive, and reversible hydrogels, we engineer novel protein-based hydrogels in this thesis. An elastomeric protein-based hydrogel is first engineered with thermo-responsive properties, which is controlled by the thermo-responsive in situ phase transition of the polypeptide side chains in the hydrogel network. Then, two dynamic hydrogels are physically cross-linked by a coiled coil interaction and a protein-protein interaction, respectively, which both exhibit time-dependent viscoelastic properties, multiple energy dissipation modes, and injectability. The viscoelastic properties of these two physically cross-linked hydrogels are stimuli-responsive due to the stimuli-responsive nature of their cross-linking methods. Finally, a light-controlled information writing approach is developed by using a light-responsive protein-protein interaction to decorate fluorescent proteins onto protein-based hydrogel blank slates. Consequently, 2D/3D fluorescence images can be produced and stored in protein-based hydrogels. The developed hydrogels are mainly responsive to temperature or light, which are two types of stimuli that have been widely adapted as therapeutic tools in biomedical studies. The stimuli-responsive property changes in the developed hydrogel systems are highly dose-sensitive and reversible, which facilitates customized fine tuning of hydrogel functionality. Therefore, we anticipate that these developed dynamic protein-based hydrogels will find various applications in biomedical studies. Moreover, the results of this thesis are expected to contribute to the quantitative prediction of dynamic hydrogel properties and inspire the bottom-up designs of other dynamic hydrogels.Science, Faculty ofChemistry, Department ofGraduat