期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：51
页码：14621-14626
DOI：10.1073/pnas.1521151113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe regular distribution of mesenchymal cells, the formation of epithelial monolayers, or their collapse into spheroidal tumors illustrates the broad range of possible organizations of cells in tissues. Unveiling a physical picture of their emergence and dynamics is of critical importance to understand tissue morphogenesis or cancer progression. Although the role of cell-substrate and cell-cell adhesion in the organization of cell colonies has been widely studied, the impact of the cell-type-specific contact inhibition of locomotion (CIL) remains unclear. Here, we include this interaction in simulations of active particles and find a number of structures and collective dynamics that recapitulate existing tissue phenotypes. We give analytical predictions for the epithelial-mesenchymal transition and the formation of 3D aggregates as a function of cell-cell adhesion and CIL strengths. Thus, our findings shed light on the physical mechanisms underlying multicellular organization. Cells in tissues can organize into a broad spectrum of structures according to their function. Drastic changes of organization, such as epithelial-mesenchymal transitions or the formation of spheroidal aggregates, are often associated either to tissue morphogenesis or to cancer progression. Here, we study the organization of cell colonies by means of simulations of self-propelled particles with generic cell-like interactions. The interplay between cell softness, cell-cell adhesion, and contact inhibition of locomotion (CIL) yields structures and collective dynamics observed in several existing tissue phenotypes. These include regular distributions of cells, dynamic cell clusters, gel-like networks, collectively migrating monolayers, and 3D aggregates. We give analytical predictions for transitions between noncohesive, cohesive, and 3D cell arrangements. We explicitly show how CIL yields an effective repulsion that promotes cell dispersal, thereby hindering the formation of cohesive tissues. Yet, in continuous monolayers, CIL leads to collective cell motion, ensures tensile intercellular stresses, and opposes cell extrusion. Thus, our work highlights the prominent role of CIL in determining the emergent structures and dynamics of cell colonies.
