Neighbor-enhanced diffusivity in dense, cohesive cell populations

• Published in: PLoS computational biology 2021-09, Vol.17 (9), p.e1009447-e1009447
• Main Authors: Lee, Hyun Gyu, Lee, Kyoung J
• Format: Article
• Language: English
• Subjects: Biological activity; Biological properties; Biology and Life Sciences; Breast cancer; Cell adhesion; Cell Adhesion - physiology; Cell Count; Cell Line, Tumor; Cell Movement - physiology; Cell Polarity - physiology; Cell populations; Cell research; Cells; Clustering; Cohesion; Computational Biology; Computer and Information Sciences; Computer Simulation; Contact inhibition; Data analysis; Diffusivity; Dispersal; Engineering and Technology; Female; Health aspects; Humans; Locomotion; Medicine and Health Sciences; Metastases; Models, Biological; Morphogenesis; Motility; Neoplasm Invasiveness - pathology; Neoplasm Invasiveness - physiopathology; Physical Sciences; Physiological aspects; Population; Research and Analysis Methods; Rotation; Spatio-Temporal Analysis; Substrates; Time-Lapse Imaging; Triple Negative Breast Neoplasms - pathology; Triple Negative Breast Neoplasms - physiopathology; Two dimensional analysis
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1009447

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.