Clustering and jamming in epithelial–mesenchymal co-cultures

Abstract

Collective behaviors emerge from coordinated cell-cell interactions during the morphogenesis of tissues and tumors. For instance, cells may display density-dependent phase transitions from a fluid-like “unjammed” phase to a solid-like “jammed” phase, while different cell types can “self-sort.” Here, we comprehensively track single cell dynamics in mixtures of sheet-forming epithelial cells and dispersed mesenchymal cells. We find that proliferating epithelial cells nucleate multicellular clusters that coarsen at a critical density, arresting migration and strengthening spatial velocity correlations. The addition of mesenchymal cells can slow cluster formation and coarsening, resulting in more dispersed individual cells with weak spatial velocity correlations. These behaviors have analogies with a jamming-unjamming transition, where the control parameters are cell density and mesenchymal fraction. This complex interplay of proliferation, clustering and correlated migration may have physical implications for understanding epithelial-mesenchymal interactions in development and disease.

Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

“…Furthermore, our predictions show that the tissue mechanics is controlled by a single fraction f r . This is consistent with recent experimental finding [64] that the fraction of mesenchymal cells can serve as a control parameter in describing jamming properties and that increasing mesenchymal fraction leads to the increase in motility. Finally, there is also experimental evidence that heterogeneity can drive more intermittent dynamics in cell migration [23].…”

Motility-limited aggregation of mammary epithelial cells into fractal-like clusters

“…S2 D and E). This relatively high size cutoff was chosen to correctly associate elongated cells with a cluster, but more compact cells within a cluster were typically located less than 50 µm apart (37). For each field of view, ∼10 clusters were typically observed, a number which remained relatively stable over ∼24 h, indicating that cells aggregated irreversibly and that clusters did not dissociate (Fig.…”

“…In the limit of higher packing densities, colloidal systems also exhibit a jamming transition as they approach random close packing, analogous to a glass transition (27). Interestingly, closely packed epithelial monolayers also exhibit arrested dynamics as they approach confluent cell densities (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). Based on these results, a jamming-like phase diagram for cell monolayers has been proposed based on cell density, cell-cell adhesion, and cell speed (40), but the importance of cell density remains unresolved since jamming can occur at constant density (35,36,39).…”

Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods

“…Unlike inert matter whose boundary conditions do not influence the internal parameters of the system, a wound that changes boundary conditions can slowly lead to decreased density and consequently unjamming 76 . The jamming/unjamming transition is also affected by the cell type: while proliferation of epithelial cells leads to migration arrest, mesenchymal cells that proliferate slower and migrate faster can impede cell jamming 77 .The underlying mechanism of the transition is proposed to be based on mechanical energy barriers to cell rearrangements, contributed by cell-cell junctions, contractile energies and adhesion energies. As the energy barriers go up, such as due to smaller adhesive with respect to contractile contributions, the systems jams.…”