Emergent Dynamics of Collective and Individual Invasion in Malignant Cancer
Ian Wong (Brown University)
Mechanics of cell sheets, multicellular assemblies and tissues
Mon 9:00 - 10:30
Barus-Holley 141
Tumor invasion and metastasis are ultimately responsible for over 90% of cancer-related fatalities, but remain poorly understood. One signature of malignant tumor progression is the detachment and dissemination of individually invading tumor cells from a collectively invading front. These complex and emergent behaviors are thought to occur as a consequence of the epithelial-mesenchymal transition (EMT), which converts adherent epithelial cells to a motile mesenchymal phenotype. Here, I integrate engineered microenvironments with high-content imaging to comprehensively measure heterogeneous invasion dynamics in populations of tens of thousands of cells. Based on their observed behaviors, cells can be clustered into distinct subpopulations that display individual or collective invasion. Remarkably, individually invading cells are associated with faster velocities as well as straighter trajectories, enabling efficient scattering and dispersal. These spatial and temporal dynamics are then physically modeled based on the solidification of binary alloys, suggesting that the governing mechanisms are differences in motility as well as phenotypic interconversion. Finally, these behaviors are perturbed using migration-inhibiting compounds, revealing that cells with different invasion phenotypes also exhibit pronounced differences in drug sensitivity.