Abstract: Cells in tissues exert forces as they squeeze, stretch, flex and pull on each other. These forces are incredibly small - on the scale of piconewtons, but they are essential in governing a cell’s survival, its proliferation, and its differentiation. A key protein responsible for sensing mechanical forces, are the cadherin family of cell-cell adhesion proteins. Cadherins are essential for the formation and maintenance of tissues; disruption in cadherin adhesion result in severe diseases like cancer and cardio-vascular disease. However, the biophysical mechanisms by which cadherins sense and respond to mechanical forces are currently unknown. My group’s research directly addresses this critical gap by integrating ultrasensitive single molecule measurements with highly predictive computer simulations. In my talk, I will show how extracellular mechanical forces change cadherin conformation on the cell surface and how these changes are regulated. Time permitting, I will also present our recent single molecule measurements, resolving prion protein misfolding, oligomerization and toxicity in neurodegenerative disease.
Biography: Sanjeevi Sivasankar is an Associate Professor in the Department of Physics and Astronomy and a Courtesy Associate Professor in the Department of Electrical and Computer Engineering and in the Department of Genetics, Development and Cell Biology at Iowa State University. He obtained his Ph.D. degree at the University of Illinois at Urbana-Champaign and then did his postdoctoral training at Stanford University. The long term goal of Sanjeevi Sivasankar’s group is to resolve the biophysical mechanisms by which cells respond to mechanical and chemical stimuli. Research in the Sivasankar group is organized around three broad themes: (i) Biophysical studies of mechanical tension sensing in cells, (ii) Single molecule biophysics technique development, and (iii) Mechanistic studies of neurotoxic protein aggregation. His research is funded by the NIH, NSF, American Cancer Society, American Heart Association, March of Dimes Foundation, and the State of Iowa.