The overarching goal of our research endeavors are to design and apply microphysiological systems ("organ-on-a-chip") to investigate features of extracellular matrix interactions and mechanobiology in normal and disease development. With respect to our cancer-related research, we have developed a "tumor-on-a-chip" model system where we can manipulate biochemical and biomechanical signals that mimic the in vivo tumor microenvironment. Using our system, we are interested in understanding how these features of the tumor microenvironment initiate metastasis, specifically metastasis of clusters of cells (collective migration). In prior studies, we identified SDF1 chemokine gradients as well as changes in interstitial fluid flow patterns that lead to directional collective migration that is led by a unique group of cells known as leader cells. We are now applying our model systems to further investigate how leader cells arise, unique phenotypes of leader cells, as well as how leader cell-stromal cell interactions alter collective migration.