Collective cell migration requires suppression of actomyosin at cell–cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells ( Dictyostelium discoideum ), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.

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P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

The Journal of Cell Biology ◽

10.1083/jcb.201505105 ◽

2016 ◽

Vol 212 (2) ◽

pp. 199-217 ◽

Cited By ~ 57

Author(s):

Cédric Plutoni ◽

Elsa Bazellieres ◽

Maïlys Le Borgne-Rochet ◽

Franck Comunale ◽

Agusti Brugues ◽

...

Keyword(s):

Cell Migration ◽

Cell Polarity ◽

Cell Biology ◽

Cell Polarization ◽

Collective Cell Migration ◽

Mechanical Forces ◽

Tumor Aggressiveness ◽

And Migration ◽

Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

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Non-junctional Cadherin3 regulates cell migration and contact inhibition of locomotion via domain-dependent opposing regulations of Rac1

10.1101/750752 ◽

2019 ◽

Author(s):

Takehiko Ichikawa ◽

Carsten Stuckenholz ◽

Lance A. Davidson

Keyword(s):

Cell Migration ◽

Contact Inhibition ◽

Cell Contact ◽

Collective Cell Migration ◽

Cell Contacts ◽

Rac1 Activity ◽

Classical Cadherins ◽

The Stability ◽

Cell Cell

AbstractClassical cadherins are well-known primary adhesion molecules responsible for physically connecting neighboring cells and signaling the cell-cell contact. Recent studies have suggested novel signaling roles for “non-junctional” cadherins (Niessen and Gottardi, 2008; Padmanabhan et al., 2017); however, the function of cadherin signaling independent of cell-cell contacts remains unknown. In this study, we used mesendoderm cells and tissues from gastrula stage Xenopus laevis embryos to demonstrate that extracellular and cytoplasmic cadherin domains regulate Rac1 in opposing directions in the absence of cell-cell contacts. Furthermore, we found that non-junctional cadherins regulate contact inhibition of locomotion (CIL) during gastrulation through alterations in the stability of the cytoskeleton. Live FRET imaging of Rac1 activity illustrated how non-junction cadherin3 (formerly C-cadherin) spatio-temporally regulates CIL. Our study provides novel insights into adhesion-independent signaling by cadherin3 and its role in regulating single and collective cell migration in vivo.

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Faculty Opinions recommendation of α-Catenin Controls the Anisotropy of Force Distribution at Cell-Cell Junctions during Collective Cell Migration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733465778.793561842 ◽

2019 ◽

Author(s):

Johan De Rooij

Keyword(s):

Cell Migration ◽

Cell Junctions ◽

Force Distribution ◽

Collective Cell Migration ◽

Cell Cell

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Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

Scientific Reports ◽

10.1038/s41598-021-83396-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoshifumi Asakura ◽

Yohei Kondo ◽

Kazuhiro Aoki ◽

Honda Naoki

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Continuum Model ◽

Tissue Level ◽

Chemical Signals ◽

Cellular Level ◽

Mathematical Framework ◽

Collective Cell Migration ◽

The Continuum ◽

Cell Cell

AbstractCollective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.

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