ABSTRACT: Cell-cell and cell-extracellular matrix mechanical interactions are fundamental to collective cell behaviors, such as migration and invasion, during tissue development, tissue repair, and cancer progression. Yet little is known about the biophysical mechanisms underlying these collective behaviors. In my talk, I will present biophysical mechanisms of cell-cell rearrangements and cell-matrix interactions using physiologically relevant 2D and 3D in vitro models and biomaterials with tunable mechanical properties. In the first part of my talk, I will present a physical mechanism for cell-cell rearrangements in epithelial monolayers. Here, I demonstrated that in contrast to the previous understanding, cell rearrangements were controlled not by cortical tension or adhesion at the cell periphery but rather by the stress fibers that produce tractions at the cell-substrate interface. In the second part, I will present my recent findings demonstrating the stiffness and mechanical plasticity of extracellular matrices, such as basement membrane (BM) and collagen-rich stroma, as key regulators of the collective invasion of breast cancer cells. Using a 3D in vitro model of collective invasion of the BM during breast cancer, I show that cells utilize both proteases and forces to breach the BM. This work establishes mechanical plasticity, in addition to stiffness, of the extracellular matrix as a significant factor in controlling the collective invasion of breast cancer. Overall, my research investigates biophysical mechanisms of collective cell behavior using pathologically relevant in vitro models and biomaterials with tunable mechanical properties.

BIO: Dr. Aashrith Saraswathibhatla is a postdoctoral researcher working with Prof. Ovijit Chaudhuri in the Mechanical Engineering department at Stanford University. His research investigates the biophysical regulation of collective invasion during breast cancer progression using mechanically tunable biomaterials, 3D in vitro models, 3D biophysical measurements, and molecular biology tools. Before his postdoc, Aashrith earned his Ph.D. from the University of Wisconsin-Madison, working with Prof. Jacob Notbohm on the role of cell forces in controlling collective cell migration in epithelial monolayers.