Fluidization of jammed epithelia by noninvasive carcinoma in a heterogeneous tumor model.

Cellular jamming has been found useful in describing biological systems, including solid tumors. We use spheroids, tumor approximations, composed of isogenic cell lines to investigate jamming across the epithelial to mesenchymal transition. In particular, we investigate spheroid fusion, which can capture both 'fluid-like' and 'solid-like' dynamics – by investigating the macroscopic dynamics of the fusion, we are able to elucidate the importance of single cell properties as well as emergent behavior. Cell shapes are found to reflect and dictate fusion capabilities. In each cell line investigated we perturb various cell properties that may influence spheroid fluidity, including nuclear stiffness and cell proliferative capacity. Additionally, we investigate the roles of cell-cell adhesion and cell contractility on fusion. These studies reveal that cell deformability promotes fusion and that increased cell-cell adhesion, and conversely decreased cell contractility, aids in jamming a spheroid system. In addition to characterizing fusion in homotypic spheroids, we also study heterotypic spheroids from the same cell lines. In this system, fluid-like cells readily fluidize otherwise solid-like spheroids and thus are able to unjam the cellular collective.