Abstract
The dispersal or mixing of cells within cellular tissue is a crucial property for diverse biological processes, ranging from morphogenesis, immune action, to tumor metastasis. With the phenomenon of 'contact inhibition of locomotion,' it is puzzling how cells achieve such processes within a densely packed cohesive population. Here we demonstrate that a proper degree of cell-cell adhesiveness can, intriguingly, enhance the super-diffusive nature of individual cells. We systematically characterize the migration trajectories of crawling MDA-MB-231 cell lines, while they are in several different clustering modes, including freely crawling singles, cohesive doublets of two cells, quadruplets, and confluent population on two-dimensional substrate. Following data analysis and computer simulation of a simple cellular Potts model, which faithfully recapitulated all key experimental observations such as enhanced diffusivity as well as periodic rotation of cell-doublets and cell-quadruplets with mixing events, we found that proper combination of active self-propelling force and cell-cell adhesion is sufficient for generating the observed phenomena. Additionally, we found that tuning parameters for these two factors covers a variety of different collective dynamic states.
Highlights
Biological cells are the fundamental building blocks of all lifeforms, ranging from single-cell animal-like amoeba to more complex multi-cellular organisms like us human beings, in which they form various organs and complex physical structures
The same study could induce a different type of transition, which the authors termed as partial epithelial-to-mesenchymal transition: Here, a chemical agent called TGF-β1 was used to transform an initial epithelial state into a hybrid state having a mixture of epithelial and mesenchymal characteristics
We provided unequivocal evidence of cell-doublet rotation, which could be viewed as a continuous sequence of cell position swapping events, rather than a steady rigid-body rotation
Summary
Biological cells are the fundamental building blocks of all lifeforms, ranging from single-cell animal-like amoeba to more complex multi-cellular organisms like us human beings, in which they form various organs and complex physical structures. Biological tissues are a collection of interacting ‘active’ cells in nonequilibrium states, in principle, cell-population can support numerous different non-epithelial dynamic states, to which an initially sedentary tissue state can switch. One of such states is flocking and a good example is the recent experimental study of Mitchel et al [19], where air pressure was used as a control parameter for transforming an airway epithelial tissue to cooperatively migratory flocking cells. The authors have concluded that UJT and pEMT, respectively, yielded two rather different liquid-like states having very divergent dynamic, structural and molecular marker characteristics. The study of Mitchel et al is an excellent example suggesting that for fully unfolding the dynamics of the dense cell population the relevant phase space needs to be at least two-dimensional (i.e., requires two independent parameters)
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