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Seminar Series “Successes and Challenges in Using Mathematical Modeling to Bridge Scales in Muscle Contraction” Sam Walcott, PhD Mathematical Sciences Worcester Polytechnic Institute Monday, September 15, 2025 GP1002 12:00pm – 12:50pm Abstract: The contraction of muscle powers vital processes like locomotion, gastric motility, and blood circulation. The rational development of therapies for dysfunction in these processes, e.g. genetic heart disease, depends on connecting molecular-scale interactions to physiological function. Since the 1950s, the sliding filament and cross bridge theories seemed to relate molecular interactions to the contraction of muscle cells. But, despite the successes of these theories, aspects of muscle contraction, e.g. the history dependence of isometric force, have eluded a mechanistic description. I'll discuss our work using mathematical modeling to bridge the molecular to cellular and larger scales. In particular, I'll share three stories: first, how we used mathematical modeling to explain how a molecular change causes fruit flies to jump further. Second, how our model of calcium activation was used to understand the mechanism of a heart drug. And third, how our modeling suggests a molecular mechanism for muscle's history dependence, and how that ties into a newly-discovered mechanism of muscle activation. Biography: (last name pronounced like the words "wall" and "cot"). I received my undergraduate degree in Biology and my PhD in Theoretical and Applied Mechanics, both from Cornell University. I did my first postdoc with David Warshaw at the University of Vermont, performing measurements in the laser trap to understand smooth muscle regulation. I did my second postdoc with Sean Sun at Johns Hopkins, developing mathematical models for cell mechanosensation. I then became an independent investigator at UC Davis in the Department of Mathematics. I am currently at Worcester Polytechnic Institute in the Department of Mathematical Sciences. My primary research interest is using mathematical modeling to tie together experimental measurements of biological systems at the molecular, cellular, and larger scales. For a zoom link please contact Kate Harrison at kharrison@wpi.edu