No abstract

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.

Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell's response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

No abstract