Advances in collective cell dynamics

Collective cell dynamics plays significant roles in various physiological or pathological processes including embryo development, wound healing, and cancer invasion. It involves the self-organization of cytoskeleton and biochemical signaling transduction, as well as complex cell-cell interactions and cell-environment interactions. Therefore, collective cell dynamics is a hot topic in the interdisciplinary fields of biology, mechanics, physics and chemistry, attracting increasing efforts, both experimentally and theoretically, toward understanding the underlying biomechanical principles. In this review, we focus on the collective cell dynamics in cell monolayer systems and introduce the research progresses in recent years. A cell monolayer refers to a single layer of cells in which cells connect to their neighbors via cell-cell adhesions and adhere to the subjacent substrate via focal adhesions. We first introduce collective cell migration modes in cell monolayer systems under various boundary constraints. In confluent cell monolayers of large size, cells always self-organize into dynamic swirling motion patterns, as observed in various cell lines. Such motion patterns stem from active cell motility and cell-cell interactions, and can be theoretically accounted for by both continuum mechanical theory such as active gel theory and discrete models such as active vertex model. Boundary constraints affect collective cell migration modes significantly. For example, for cell monolayers in confined spaces, the persistent rotation mode, the collectively directed motion mode, and the shear flow mode have been observed. While for freely expanding cell monolayers, deformation waves emerge spontaneously and propagate toward the interior region of the cell monolayer. As a confluent cell monolayer matures, the cell density increases while cell motions gradually slow down, indicating a jamming-like behavior. Such jamming-like behavior of collective cell migration has been suggested similar to the jamming behavior of particle systems. We next introduce the statistics of cell shape and cell orientation, and discuss the relation between collective cell migration, cell fate and topological defects formed by cell orientation. Specifically, reported experiments indicated that in two-dimensional cell monolayers +1/2 topological defects trigger cell accumulation or cell extrusion while −1/2 topological defects lead to cell escape, accompanied with distinct tissue flow patterns. This topological defect-dictated cell fate has been observed in both eukaryotic cell monolayers and bacterial suspensions, revealing its potential universality. We further introduce collective cell shape oscillations and the underlying biomechanical mechanisms. Cell shape oscillation has been observed in both isolated cell systems and collective cell systems, stemming from the negative feedback between myosin activity and cell deformation. Compared with isolated cell oscillations, collective cells exhibit coordinated oscillatory morphodynamics, including aligned oscillatory patterns, polarized oscillation directions, and synchronized oscillatory amplitudes, which may help signaling transmission and synchronization among cells over large scales. In addition, collective cell dynamics on curved substrates and the role of substrate curvature is briefly introduced. This topic is in its infancy and plenty of questions remain to be explored. Finally, we introduce the cellular vertex model, an extensively used mechanical model in the study of epithelial mechanics and collective cell dynamics. In the cellular vertex model, cells are represented by interconnected polygons and vertices refer to tri-cellular junctions. The history, development, theoretical foundation, and applications of the cellular vertex model are briefly introduced.