Directed persistent motion maintains sheet integrity during multi-cellular spreading and migration

Nnetu, Kenechukwu David; Knorr, Melanie; Strehle, Dan; Zink, Mareike; Käs, Josef A.

doi:10.1039/c2sm07208d

Cited by 35 publications

(32 citation statements)

References 48 publications

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“…Chemicals such as trypsin down-regulate intercellular interactions and change the physical properties of the monolayer, especially the line tension, preventing cells from escaping the sheet. In contrast, fibroblast cells were shown not to migrate collectively; single cells detach from the monolayer and no smooth cell front is sustained [11,12].…”

Section: Introductionmentioning

confidence: 95%

“…Although intercellular interactions are important in maintaining the integrity of a migrating cell monolayer, the dynamic interplay between escaping single cells and the monolayer is also sufficient to maintain a constant cell front during collective cell migration. It was recently shown with a wound-healing-like assay that cells collectively migrating into free space move ballistically, while escaping single cells migrate randomly on long times [12]. This ballistic motion of the monolayer allows it to catch up with escaping single cells and a constant boundary and line tension during migration is observed.…”

Section: Introductionmentioning

confidence: 97%

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

et al. 2012

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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.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 97%

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

et al. 2012

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“…Alternately, many studies have explored the expansion of tissues that initially grow into confluence within confinement but are later allowed to migrate into free space upon removal of a barrier. A popular assay of this type relies on rectangular strips of tissue that are allowed to expand in one or both directions (13)(14)(15)(16)(17)(18)(19)(20)(21), where averaging along the length of the strip can reveal coordinated population-level behaviors such as complex migration patterns, non-uniform traction force fields, and traveling mechanical waves. Isotropic expansion has also been studied in the context of micro-scale (< 500 µm diameter) circular tissues using the barrier stencil technique (22) as well as photoswitchable substrates (23), revealing behaviors associated with initial expansion of a tissue.…”

Section: Introductionmentioning

confidence: 99%

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Heinrich

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LaChance

et al. 2020

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In the last decade, key advances in our understanding of collective cell migration and tissue growth have been made by studying the expansion of epithelial monolayers in vitro. However, most studies have focused on monolayers of sub-millimetric sizes, and how cell proliferation and migration are coordinated on larger scales remains poorly known. To fill this gap, we measured cell velocity, cell density, and cell-cycle state over 2 days in millimeter-scale freely-expanding monolayers. We find that tissues of different initial sizes exhibit very different spatiotemporal patterns of cell proliferation and collective cell migration in their internal regions. Specifically, within several cell cycles, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, the core of smaller tissues develops a local minimum of cell density as well as a tissue-spanning vortex. These different dynamics are determined not by the current but by the initial tissue size, indicating that the state of the tissue depends on its history. Despite these marked differences at the internal regions, the edge zone of both large and small tissues displays rapid cell-cycle progression and radially-oriented migration with a steady velocity independent of tissue size. As a result, the overall area expansion rate is dictated by the perimeter-to-area ratio of the tissue. Our findings suggest that cell proliferation and migration are regulated in a collective manner that decouples the internal and edge regions of the tissue, which leads to size-and history-dependent internal patterns in expanding epithelia. tissue growth | cell cycle | collective migration | epithelia

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“…However, the predictive value of these assays is controversial, particularly if cell lines with different genetic background are compared. More recently, time-lapse imaging and subsequent image analysis using particle image velocimetry (PIV) to quantify cell motion have provided a more revealing view of collective cell migration, especially in the context of unconstrained migration assays [34], [35], [36], [37]. Such methodologies will greatly expand our understanding of how both intrinsic and extrinsic factors contribute to invasive migratory behaviors observed in many cancers, including breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Motion Analysis Reveals Cell Directionality as an Indicator of Breast Cancer Progression

et al. 2013

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Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV) to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF) or lysophosphatitic acid (LPA) are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.

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Directed persistent motion maintains sheet integrity during multi-cellular spreading and migration

Cited by 35 publications

References 48 publications

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

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

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Real-Time Motion Analysis Reveals Cell Directionality as an Indicator of Breast Cancer Progression

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