MSE Seminar: “Harnessing Temporally Controlled Biophysical Cues To Direct Stem Cell Phenotype”

Endogenous tissue-specific stem cells are crucial regulators of tissue health throughout life, orchestrating diverse functions ranging from learning and cognition to skeletal muscle homeostasis. The local microenvironment, or stem cell niche, presents a myriad of biochemical and biophysical factors that direct cell fate. Stem cell mediated tissue regeneration relies on presentation of these factors in a precise temporal sequence at appropriate doses. Dysregulation of this process, such as in aging and disease, leads to diminished tissue function and potentially organ failure. Despite the known importance of biophysical cues in regulating stem cell phenotype, the effects of temporal changes in the mechanical and microstructural properties of the extracellular matrix (ECM) on stem cell fate remain poorly understood, in large part due to a lack of suitable engineered systems to selectively probe how changing matrix properties impact cellular signaling. In my talk, I will describe a multifaceted strategy to elucidate unappreciated mechanisms behind cell-ECM interactions impacting homeostasis and disease, drawing on protein engineering, bioorthogonal chemistries, and stem cell biology. In the first half of the talk, I will discuss the use of protein engineered biomaterials to identify critical ECM properties that are required for neural stem cell expansion. The second half of the talk will focus on the development of bioorthogonal chemical strategies to regulate the mechanical properties of synthetic cell culture substrates on demand and the application of these materials to determine how temporally varying matrix properties impact muscle stem cell commitment. Together, these research projects highlight the power of engineered platforms in elucidating novel biological mechanisms implicated in development, disease, and aging.