Many proteins, particularly those in fibrous extracellular and intracellular structures participate in load bearing and mechanotransduction – the process of converting mechanical signals into biochemical action, in the body. Studies have shown that cell and tissue mechanics strongly influence cell behaviors, and recent work has highlighted the role of fibrous nature of these networks in mechanotransduction. What if the proteins that compose the extracellular matrix or the intracellular cytoskeleton are themselves mechanotransducers? In this talk, I will present our work over the last years using in situ advanced microscopy to quantify protein structure in fibrous protein biomaterials in situ under different mechanical loads. We use label-fee molecular microscopy and Förster resonance energy transfer microscopy to measure protein structure in fibrin ECM and vimentin networks. Our results on fibrin show that fibrin hydrogels develop previously undetected microscale spatial-structural heterogeneity in response to tension that is not present in the unloaded state. Combining this methodology with isotopic exchange, we demonstrate the ability to measure secondary structure of vimentin intermediate filaments in cells. Ultimately, we aim to understand how molecular changes in protein secondary structure of load-bearing structures controls physiological function.

Sapun Parekh is an Assistant Professor of Biomedical Engineering at UT Austin. At UT, his group focuses on molecular microscopy, and his research interests include applications and development of nonlinear microscopy, chemical imaging of neurodegeneration and cancer, and molecular biophysics.
Sapun completed his BS in Electrical Engineering from the University of Texas at Austin in 2002 and his PhD in Bioengineering from the University of California at Berkeley/San Francisco in 2008. His PhD thesis focused on force generation and mechanics of semi-flexible actin networks that are ubiquitous in biology via atomic force microscopy (AFMs) using home-built AFMs that had improved long-term stability. After his PhD, he was a National Research Council postdoctoral fellow in the Biomaterials Group at the National Institute for Standards and Technology where he worked on mechanobiology of stem cell differentiation and development of label-free imaging techniques. Following his postdoc, he worked as a Science Policy Fellow in the National Science Foundation in Washington, DC and as a visiting scientist at the National Institutes of Health on super resolution imaging. He then joined the Max Planck Institute for Polymer Research as a founding member of the Department of Molecular Spectroscopy in February 2012. As of January 2019, he is an assistant professor in the Department of Biomedical Engineering at UT Austin UT and an adjunct group leader at the Max Planck Institute.