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Collective cell migration is extensively observed in embryo development and cancer invasion. During these processes, the interactions between cells with distinct identities and fates are of importance for boundary formation and host defense against cancer. In this paper, we explore the collective dynamics of a two-dimensional cell mixing monolayer consisting of non-tumorigenic mammary epithelial cells and breast cancer cells. We show that the epithelial–cancerous cell mixing system displays unique sorting behaviors. The epithelial cells aggregate to form scattered clusters, which perform random motion with simultaneous translation and rotation, strikingly distinct from the classical persistent random walk of individual migratory cells. The motility of cancer cells is markedly promoted by the epithelial clusters, exhibiting remarkable contact enhancement of locomotion. A discrete model based on the Johnson–Kendall–Roberts contact mechanics is proposed to identify the influence of intercellular interactions, active migration forces and cell–substrate friction forces on the collective cell dynamics. These findings could advance our understanding of many biological processes, such as cancer metastasis and tissue morphogenesis. The epithelial–cancerous cell mixing system displays unique collective dynamics. The epithelial cells aggregate to form scattered clusters, which perform random motion with simultaneous translation and rotation, strikingly distinct from the classical persistent random walk of individual migratory cells. The interactions between the two cell types drive the evolution of collective migration dynamics and give rise to a behavior akin to the contact enhancement of locomotion. This study revealed the distinctive dynamic features and the underlying regulatory mechanisms arising from epithelial–cancerous interactions. [ABSTRACT FROM AUTHOR]

Computational models of cell-cell mechanical interactions typically simulate sorting and certain other motions well, but as demands on these models continue to grow, discrepancies between the cell shapes, contact angles and behaviours they predict and those that occur in real cells have come under increased scrutiny. To investigate whether these discrepancies are a direct result of the straight cell-cell edges generally assumed in these models, we developed a finite element model that approximates cell boundaries using polylines with an arbitrary number of segments. We then compared the predictions of otherwise identical polyline and monoline (straight-edge) models in a variety of scenarios, including annealing, single- and multi-cell engulfment, sorting, and two forms of mixing-invasion and checkerboard pattern formation. Keeping cell-cell edges straight influences cell motion, cell shape, contact angle, and boundary length, especially in cases where one cell type is pulled between or around cells of a different type, as in engulfment or invasion. These differences arise because monoline cells have restricted deformation modes. Polyline cells do not face these restrictions, and with as few as three segments per edge yielded realistic edge shapes and contact angle errors one-tenth of those produced by monoline models, making them considerably more suitable for situations where angles and shapes matter, such as validation of cellular force-inference techniques. The findings suggest that non-straight cell edges are important both in modelling and in nature. [ABSTRACT FROM AUTHOR]

During animal development, tissues and organs are partitioned into compartments that do not intermix. This organizing principle is essential for correct tissue morphogenesis. Given that cell sorting defects during compartmentalization in humans are thought to cause malignant invasion and congenital defects such as cranio-fronto-nasal syndrome, identifying the molecular and cellular mechanisms that keep cells apart at boundaries between compartments is important. In both vertebrates and invertebrates, transcription factors and short-range signalling pathways, such as EPH/Ephrin, Hedgehog, or Notch signalling, govern compartmental cell sorting. However, the mechanisms that mediate cell sorting downstream of these factors have remained elusive for decades. Here, we review recent data gathered in Drosophila that suggest that the generation of cortical tensile forces at compartmental boundaries by the actomyosin cytoskeleton could be a general mechanism that inhibits cell mixing between compartments. [ABSTRACT FROM AUTHOR]