Pharmacological Regulation of Protein-Polymer Hydrogel Stiffness

Thesis (Master's)--University of Washington, 2020The extracellular matrix (ECM) exhibits constant physiochemical changes throughout all biological processes, including organ development, maintenance of tissue homeostasis, and disease progression/ healing. User-programmable biomaterials afford exciting opportunities to study such dynamic processes in vitro, offering a means to probe biological fates in response to biochemical and biophysical changes in the ECM. Herein, we introduce a protein-polymer hydrogel biomaterial whose stiffness can be pharmacologically regulated with conventional antibiotics, providing a powerful first route to stimulate synthetic tissue changes in vivo. Specifically, a coumermycin-mediated homodimerization of DNA gyrase subunit B (GyrB) tethered within the gel enables user-modulated physical crosslinking and a rheological increase in hydrogel mechanics. These unique platforms will prove useful in elucidating the effects of ECM-presented mechanical signals on cell function