Abstract: Cells exist in a complex mechanical environment that is a source of applied forces and a means of mechanical support. Cells respond to these mechanical signals through a poorly understood process called mechanotransduction. A clearer understanding of this process will lead to improved methods for manipulating cell behavior in engineered tissues and increased understanding of mechanosensitive disease states, such as atherosclerosis and cancer. As mechanotransduction is likely due to force-induced conformation changes in load-bearing proteins, we develop and use protein-based biosensors that exhibit force-dependent changes in the color of emitted light. This technology enables dynamic measurements of mechanical forces at the molecular level that are innately compatible with concepts and approaches common in molecular biology and biophysics, uniquely enabling mechanistic studies of mechanotransduction. The current challenge is developing approaches that reveal the effects of mechanical loading on protein function in living cells. In this talk, I will discuss our efforts to develop new assays for probing the relationship between protein load and the composition of key sub-cellular structures as well as the relationship between protein loading and protein dynamics. I will conclude with a discussion of how these techniques are changing our understanding of the mechanisms cells use to detect and respond to mechanical cues.

Dr. Brenton Hoffman is an Assistant Professor in the Department of Biomedical Engineering at Duke University where he is the principal investigator of the Cell and Molecular Mechanobiology Laboratory. He received a B.S. Degree in Chemical Engineering from Lehigh University, a PhD in Chemical and Biomolecular Engineering from the University of Pennsylvania, and completed Post-doctoral training in the Cardiovascular Research Center at the University of Virginia. Dr. Hoffman’s current research interests are in the areas of cell mechanics, cell migration, and mechanotransduction, with a particular focus on the development of new tools and approaches for studying the effects of mechanical loading on protein function in living cells. His lab has received funding from the National Science Foundation, the National Institutes of Health, and the American Heart Association. He has been awarded a Basil O’Connor Starter Scholar Award from the March of Dimes, a Searle Scholar Award, and NSF CAREER Award. He has also received the Klein Family Distinguished Teaching Award, the highest award in Duke’s Pratt School of Engineering for teaching.