Journal ArticleDOI
A molecular mechanotransduction pathway regulates collective migration of epithelial cells
TLDR
It is shown that a tumour suppressor protein, merlin, coordinates collective migration of tens of cells, by acting as a mechanochemical transducer in a stationary epithelial monolayer and in three-dimensional human skin.Abstract:
Collective movement of epithelial cells drives essential multicellular organization during various fundamental physiological processes encompassing embryonic morphogenesis, cancer and wound healing. Yet the molecular mechanism that ensures the coordinated movement of many cells remains elusive. Here we show that a tumour suppressor protein, merlin, coordinates collective migration of tens of cells, by acting as a mechanochemical transducer. In a stationary epithelial monolayer and also in three-dimensional human skin, merlin localizes to cortical cell-cell junctions. During migration initiation, a fraction of cortical merlin relocalizes to the cytoplasm. This relocalization is triggered by the intercellular pulling force of the leading cell and depends on the actomyosin-based cell contractility. Then in migrating cells, taking its cue from the intercellular pulling forces, which show long-distance ordering, merlin coordinates polarized Rac1 activation and lamellipodium formation on the multicellular length scale. Together, these results provide a distinct molecular mechanism linking intercellular forces to collective cell movements in migrating epithelia.read more
Citations
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The front and rear of collective cell migration
TL;DR: The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement.
Journal ArticleDOI
Mechanobiology of collective cell behaviours.
Benoit Ladoux,René-Marc Mège +1 more
TL;DR: This work has shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces.
Journal ArticleDOI
Quantifying forces in cell biology
TL;DR: As mechanics is increasingly revealed to play a fundamental role in cell function it is envisage that tools to quantify physical forces may soon become widely applied in life-sciences laboratories.
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Collective cell migration: guidance principles and hierarchies
TL;DR: This work reviews mechanochemical and electrical inputs and multiparameter signal integration underlying collective guidance, decision making, and outcome of collective cell migration.
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Collective cell migration in development
Elena Scarpa,Roberto Mayor +1 more
TL;DR: Recent advances in understanding collective migration in developmental models are reviewed, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective.
References
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Journal ArticleDOI
Role of YAP/TAZ in mechanotransduction
Sirio Dupont,Leonardo Morsut,Mariaceleste Aragona,Elena Enzo,Stefano Giulitti,Michelangelo Cordenonsi,Francesca Zanconato,Jimmy Le Digabel,Mattia Forcato,Silvio Bicciato,Nicola Elvassore,Stefano Piccolo +11 more
TL;DR: YAP/TAZ are identified as sensors and mediators of mechanical cues instructed by the cellular microenvironment and are functionally required for differentiation of mesenchymal stem cells induced by ECM stiffness and for survival of endothelial cells regulated by cell geometry.
Journal ArticleDOI
Collective cell migration in morphogenesis, regeneration and cancer
Peter Friedl,Darren Gilmour +1 more
TL;DR: Comparing different types of collective migration at the molecular and cellular level reveals a common mechanistic theme between developmental and cancer research.
Journal ArticleDOI
Local force and geometry sensing regulate cell functions.
Viola Vogel,Michael P. Sheetz +1 more
TL;DR: Tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms of eukaryotic cells.
Journal ArticleDOI
Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells.
Cedric Gaggioli,Steven Hooper,Cristina Hidalgo-Carcedo,Robert Grosse,John Marshall,Kevin J. Harrington,Erik Sahai +6 more
TL;DR: Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals that the leading cell is always a fibroblast and that carcinomas cells move within tracks in the extracellular matrix behind the fibro Blast.
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Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics
Carsten Grashoff,Brenton D. Hoffman,Michael D. Brenner,Ruobo Zhou,Madeline Parsons,Michael T. Yang,Mark A. McLean,Stephen G. Sligar,Christopher S. Chen,Taekjip Ha,Taekjip Ha,Martin A. Schwartz +11 more
TL;DR: Developing a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity reveals that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently.