Mechanical regulation of collective behavior and interfacial dynamics of cell clusters

Abstract

Cells frequently exist in clusters throughout the body and establish a boundary to the surrounding environment in various pathophysiological processes. For instance, heterotypic cells differentiate into a certain tissue by forming and maintaining a boundary during development, and the wound presents the boundary between cells and vacant matrixes. The boundary is an intriguing domain with a sharp asymmetry caused by differences between the internal conditions within the cell cluster and the external environment, which may include heterotypic neighbors or empty spaces. Biophysical asymmetry at the boundary can alter cellular behaviors because the cell is an active matter that exhibits dynamics in response to its environment. Motility and forces, two key dynamic quantities in cellular responses, are intricately entangled to determine tissue-scale phenotypic changes. To decode the complex correlations between boundary asymmetry and cell behaviors, various boundaries of the cell clusters were investigated by utilizing microscopic image-based visualization techniques for motions and stresses. The collective cell migration behavior was first identified as being regulated by the geometry of the free boundary, and then the propagation of boundary movement into the interior cells was also analyzed. Finally, the physical interfaces between heterotypic cells were investigated as another type of external boundary of cell clusters. All these suggested approaches have a certain potential for spatiotemporally quantifying cellular functions during the development step of disease models and cell therapies. The quantified information on cellular dynamics will serve as the foundation for data-driven cell evaluation technology.