Abstract

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.

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