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UBC Theses and Dissertations

Engineering globular protein-based hydrogels with tunable mechanical properties Fu, Linglan


Most recently, hydrogels composed of recombinant proteins/peptides have attracted great interest due to their diverse biofunctions, designable amino acids sequence, reactive side chains, excellent biocompatibility and biodegradability. Moreover, conformational switching of folded proteins induces structural and thermodynamic changes in the network, leading to dynamic properties and energy dissipative ability of hydrogels. Despite these advantages, applications of recombinant protein-based hydrogels are often limited by their poor mechanical performance and inefficient network crosslinking, due to steric hindrance of bulky protein domains in the networks. To optimize mechanical behaviors of structural protein-based hydrogels, it is important to understand the design principles of globular protein-based elastomeric networks. This thesis discusses the latest research on protein-based hydrogels, including network designs, crosslinking strategies, and resulting physical and mechanical features of the materials. In addition, classic rubber elasticity theory is introduced to reveal the effects of elastomeric network on physical and mechanical properties of synthetic polymer hydrogels. Based on the theory, a semi-quantitative tool was developed to predict/explain mechanical properties of globular folded polyprotein-based hydrogels, providing guidance for the rational design of globular polyprotein-based hydrogels with desired mechanical properties. Furthermore, we demonstrate for the first time that the macroscopic mechanical energy generated from conformational change of globular proteins closely corresponds to single molecule mechanochemical events by investigating mechanochemical coupling cycles of globular folded proteins at both single-molecule and macroscopic levels. With the guidance of the design principle, we describe synthesis of super tough protein-based hydrogels based on a novel denatured-crosslinking hydrogelation method, which provides potential cartilage-like biomaterials and a general strategy for mechanical enhancement for protein-based hydrogels. We also explored the synthesis of super tough protein-alginate hybrid hydrogels using a double-network approach, further broadening the range of mechanical properties that protein-based biomaterials can reach. Taking advantage of precise mechanical control and dynamic behaviors of mutually exclusive protein-based hydrogels, an application of protein-based hydrogels is reported as extracellular matrices for cell spreading studies, demonstrating a great potential utility of dynamic protein hydrogels in cellular mechano-biology studies.

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