Abstract A63: Collective and individual migration after the epithelial-mesenchymal transition in engineered microenvironments

Abstract

Abstract Scattering and local dissemination of individual cells from a collective invasion front has been associated with the epithelial-mesenchymal transition (EMT). This phenotypic heterogeneity and plasticity has been challenging to reconstruct using classical assays which only measure population averages at endpoints. Here, we comprehensively track single cell invasion dynamics within engineered microenvironments such as microfabricated pillar arrays as well as 3D biomaterial scaffolds. After EMT induction through the master regulator Snail in mammary epithelial cells, we find distinct phenotypic subpopulations that display collective or individual migration behaviors. We show that these complex behaviors can be physically understood in terms of a phase transition during the solidification of binary alloys. Biologically, this conceptual framework addresses two essential mechanisms—phenotypic cell sorting and interconversion. We present new results to corroborate this model by systematically varying the composition of mosaic populations with both epithelial and EMT phenotypes. We also perturb these behaviors using migration-inhibiting compounds, revealing that different invasion phenotypes are correlated with differences in drug sensitivity. Altogether, this integration of engineered microenvironments with single cell resolution may permit new quantitative insights into the interplay of invasion, drug resistance and heterogeneity. Citation Format: Ian Y. Wong. Collective and individual migration after the epithelial-mesenchymal transition in engineered microenvironments. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A63.