Understanding the mechanics and dynamics of active matter at high density is indispensable to a range of physical and biological processes such as swarm dynamics, tissue formation and cancer metastasis. Here, we study the dynamics and mechanics of an MCF-10A epithelial cell monolayer on the multi-cellular and single-cell scales and over a wide density range. We show that the dynamics and Young's modulus of the monolayer are spatially heterogeneous on the multi-cellular scale. With increasing cell density, the monolayer approached kinetic arrest and the Young's modulus scaled critically. On the single-cell scale, as the cell density increased, cells were intermittently trapped in cages formed by their neighbors and their motion evolved from a ballistic motion to a sub-diffusive motion. Furthermore, the relaxation time and inverse self-diffusivity increased exponentially with the cell density. These findings provide a mechanism for long-ranged mechanical stress propagation, tissue remodeling and patterning at very high cell densities.
Collective cell migration is an important feature of wound healing, as well as embryonic and tumor development. The origin of collective cell migration is mainly intercellular interactions through effects such as a line tension preventing cells from detaching from the boundary. In contrast, in this study, we show for the first time that the formation of a constant cell front of a monolayer can also be maintained by the dynamics of the underlying migrating single cells. Ballistic motion enables the maintenance of the integrity of the sheet, while a slowed down dynamics and glass-like behavior cause jamming of cells at the front when two monolayers-even of the same cell type-meet. By employing a velocity autocorrelation function to investigate the cell dynamics in detail, we found a compressed exponential decay as described by the Kohlrausch-William-Watts function of the form C(δx) t ∼ exp (−(x/x 0 (t)) β(t) ), with 1.5 β(t) 1.8. This clearly shows that although migrating cells are an active, non-equilibrium system, the cell monolayer behaves in a glass-like way, which requires jamming as a part of intercellular interactions. Since it is the dynamics which determine the integrity of the cell sheet and its front for weakly interacting cells, it becomes evident why changes of the migratory behavior during epithelial to mesenchymal transition can result in the escape of single cells and metastasis.
The lamellipodium, a thin veil-like structure at the leading edge of motile cells, is fundamental for cell migration and growth. Orchestrated activities of membrane components and an underlying biopolymer film result in a controlled movement of the whole system. Dynamics in two-dimensional cell motility are primarily driven by the actively moving protein film in the lamellipodium. Polymerization of actin filaments at the leading edge, back-transport of the actin network due to myosin motor activity, depolymerization in the back, and diffusive transport of actin monomers to the front control these dynamics. The same molecular prerequisites for lamellipodial motion are found in most eukaryotic cells and can function independently of the cell body. Here we show that lamellipodial dynamics differ strongly in different cell types according to their function. Path finding neuronal growth cones display strong stochastic fluctuations, wound healing fibroblasts that locally migrate in tissues exhibit reduced fluctuations while fish keratocytes move highly persistently. Nevertheless, experimental analysis and computer simulations show that changes in the parameters for actin polymerization and retrograde actin transport alone are sufficient for the cell to utilize the same, highly adaptive machinery to display this rich variety of behaviors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.