Title: Cell-Matrix Interactions in Cancer and Fibrosis: Multiscale Chemo-Mechanical Models
Speaker: Professor Vivek Shenoy, School of Engineering and Applied Sciences, University of Pennsylvania
Abstract:
Cell invasion into the surrounding matrix from non-vascularized primary tumors is the main mechanism by which cancer cells migrate to nearby blood vessels and metastasize to eventually form secondary tumors. This process is mediated by an intricate coupling between intracellular and extracellular forces that depend on the stiffness of the surrounding stroma and the alignment of matrix fibers. A multiscale model is used to elucidate the two-way feedback loop between stress-dependent cell contractility and matrix fiber realignment and strain stiffening, which enables the cells to polarize and enhance their contractility to break free from the tumor and invade into the matrix. Importantly, our model can be used to explain how morphological and structural changes in the tumor microenvironment, such as elevated rigidity and fiber alignment prior to cell invasion, are prognostic of the malignant phenotype. The model also predicts how the alignment of matrix fibers can recruit ma crophages, which are among the first responders of the innate immune system following organ injury and are crucial for repair, resolution, and re-establishing homeostasis of damaged tissue. I will discuss how the deformation of the nucleus during migration can lead to changes in the spatial organization of chromosomes and their intermingling which can result in genetic mutations and genomic instability. I will also discuss how targeting extracellular matrix mechanics, by preventing or reversing tissue stiffening or interrupting the cellular response in cancer and fibrosis, is a therapeutic approach with clinical potential.
BIO: Vivek Shenoy is the Eduardo D. Glandt President’s Distinguished Professor in the School of Engineering and Applied Sciences at the University of Pennsylvania. Dr. Shenoy's research focuses on developing theoretical concepts and numerical methods to understand the basic principles that control the behavior of both engineering and biological systems. He has used rigorous analytical methods and multiscale modeling techniques, ranging from atomistic density functional theory to continuum methods, to gain physical insight into a myriad of problems in materials science and biomechanics. Dr. Shenoy's honors include a National Science Foundation CAREER Award (2000), the Richard and Edna Solomon Assistant Professorship (2002-2005) and the Rosenbaum Visiting Fellowship from the Isaac Newton Institute of Mathematical Science, University of Cambridge and the Heilmeier award for excellence in faculty research (2019). He is the principal investigator and director of the NSF-f unded Science and Technology Center for Engineering Mechanobiology established in 2016. He also serves the editor of the Biophysical Journal and is a fellow of the American Institute for Medical and Biological Engineering (AIMBE).
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