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Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

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Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating… Click to show full abstract

Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.Mechanobiology: Division of forces across a cell monolayerCells sense their extracellular environment using focal adhesions, which can be imagined as mechanical linkages. While mechanobiological research mostly focuses on single cells, a team led by Sulin Zhang at Pennsylvania State University explored how multicellular ensembles transmit and distribute traction forces. The authors develop a thermodynamic model and validate predictions by experimental measures including traction force microscopy. They find that at the monolayer outline focal adhesions generate high traction force through interaction with the extracellular substrate, whereas cells in the centre of the sheet experience low traction force but have elevated cellular stress levels. This model will help to decipher how the local environment influences cellular decisions and will spur research on more complex problems of epithelial tissues, such as morphogenesis or collective migration.

Keywords: microscopy; landscapes cohesive; force; traction; cellular force; force landscapes

Journal Title: npj Computational Materials
Year Published: 2018

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