Probing the Effects of Molecular Tension on Protein Function in Cellulo

Speaker: Brenton Hoffman, Ph.D.

Abstract:

In vivo, 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 stimuli through a poorly understood process called mechanotransduction. A clearer understanding of this process will lead to improved methods for manipulating cell behavior in the contexts of engineered tissue constructs as well as mechanically sensitive disease states (e.g., cancer and atherosclerosis). 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, enabling mechanistic studies of mechanotransduction. An emerging limitation in the study of mechanotransduction is the incompatibility of commonly used experimental techniques with systems biology approaches. This deficiency is likely preventing an understanding of how mechanical stimuli induce coordinated changes across cell signaling networks to drive significant changes in cell behavior (e.g. migration, differentiation, and growth). In this talk, I will discuss how we have been expanding the use of biosensors to understand the effects of force on protein function in cells. Specifically, I will focus on our efforts to leverage quantitative imaging approaches and other techniques (e.g. proximity proteomics and Markov Chain-based modeling of mechanotransduction within cell adhesions) to begin to develop molecular systems mechanobiology.

Speaker Bio:

Dr. Brenton Hoffman is the James L. and Elizabeth M. Vincent Associate Professor of Biomedical Engineering at Duke University. He received a B.S. Degree in Chemical Engineering from Lehigh University, earned 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 (2013), a Searle Scholar Award (2013), and NSF CAREER Award (2015). He has also received the Klein Family Distinguished Teaching Award in Duke’s Pratt School of Engineering for excellence in teaching (2016), was named a Duke Bass Fellow for excellence in research and undergraduate instruction (2020), and received the Iwao Yasuda Award for excellence in service to the Cell and Molecular Bioengineering Special Interest Group of the Biomedical Engineering Society (2022).

Host: Gaudenz Danuser, Ph.D.