2018 SEED project summary: Collectively migrating cells sense matrix stiffness through adhesions and cytoskeletal forces. We have recently shown that mechanical priming of epithelial cells on a stiff ECM enhances their future migration, even after they move to a soft ECM. This storage of past mechano-activation in migratory cells depends on nuclear YAP localization. In this project, we investigate biophysical mechanisms that connect nuclear YAP to cellular forces and collective cell migration. Based on experimental findings, we are also building a computational framework for collective cell migration across matrices of dissimilar stiffness through rate-dependent mechanotransduction. Through this integrated approach, we aim to understand how mechanical priming and memory might be regulated by the crosstalk of nucleus shape, YAP localization, cytoskeletal machinery, and cell migration, all operating at multiple time and length scales.
2018 SEED Grant Recipient