Abstract

One of the most fascinating and important processes in biology and medicine is the transformation of a stem cell system into mature tissue cells; this change, called differentiation, consists of a progression of highly regulated steps. Despite its importance both for bringing comprehension to the formation of the embryo and also for regenerative medicine purposes, the ways in which the process of differentiation are regulated – which have been primarily studied from a biochemical perspective – are poorly understood. We are particularly focused on illuminating differentiation and embryonic development by utilising optical, quantitative microscopy, and microfluidic techniques to probe biophysical aspects. These aspects include system level changes such as cell and nuclear mechanics, subcellular structure, and dynamic processes such as remodeling within cell nuclei. Using this foundation, we have observed broad biophysical changes in embryonic stem cells as they go through the process of differentiation; these changes include a modulation of nuclear substructure and mechanics, among others. I will discuss these results and strategies for discovering the meaning of these changes, both in stem cell cultures and in the embryo, and their universality in other developmental niches. Finally, I will discuss biotechnology we are developing to assess biophysical phenotypes and their mechanisms in stem cell systems with comprehensive applicability to other biological systems.