Institute for Stem Cell & Regenerative Medicine

at the University of Washington

2015 Jaconette L. Tietze Young Scientist Research Award

Cole DeForest, PhD, Assistant Professor,
Chemical Engineering

Spatiotemporal regulation of Notch signaling via site-specific immobilization of full-length Delta-1 protein

The extracellular matrix directs stem cell function through a complex choreography of biomacromolecular interactions in a tissue-dependent manner. Far from static, this hierarchical milieu
of biochemical and biophysical cues presented within the native cellular niche is both spatially-complex and ever-changing. As these pericellular reconfigurations are vital for tissue morphogenesis, disease regulation, and healing, in vitro culture platforms that recapitulate such dynamic environmental phenomena would be invaluable for fundamental studies in stem cell biology, as well as in the eventual engineering of functional human tissue. Preliminary efforts in this regard by our group and others have largely focused on the exploitation of photochemical-based techniques to tether bioactive small molecules and peptides spatially within synthetic hydrogel culture systems. While such approaches have indeed proven successful in directing 3D cell physiology, the realized biological control has been confined to relatively simple cellular functions (e.g., adhesion, proliferation). In order to govern and assay more complex decisions of fate than those accessible through small-molecule and peptide-based approaches, a system that enables dynamic presentation of full-length proteins would be of great interest. In this project, we will develop a robust synthetic strategy enabling the user-defined immobilization of physiologically-relevant proteins of interest in a site-specific manner within a 3D cell culture platform. The developed strategies will be utilized to direct stem cell-derived cardiomyocyte differentiation and proliferation by activation of the Notch signaling pathway via the spatiotemporally-patterned tethering of Delta-1 protein, providing novel insight into stem cell physiology and potential in translational medicine.