The impact of jamming on boundaries of collectively moving weak-interacting cells

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/x0(t))β(t)), with 1.5 6 β(t) 6 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

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

The impact of jamming on boundaries of collectively moving weak-interacting cells

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/x0(t))β(t)), with 1.5 6 β(t) 6 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 impact of jamming on boundaries of collectively moving weak-interacting cells

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/x0(t))β(t)), with 1.5 6 β(t) 6 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

Actin and microtubule networks contribute differently to cell response for small and large strains

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(\u845% 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 microtubule

Actin and microtubule networks contribute differently to cell response for small and large strains

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(\u845% 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 microtubule