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bioRxiv · 10.1101/2022.10.22.513348

A fast yet force-effective mode of collective cell migration on aligned fibers due to rapid stabilization of contractile forces

Bagchi, A.·Sarker, B.·Zhang, J.·Foston, M.·Pathak, A.
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Abstract

Cell collectives, like other motile entities, generate and use forces to move forward. Here, we ask whether environmental configurations alter this proportional force-speed relationship, since aligned extracellular matrix fibers are known to cause directed migration. We show that aligned fibers serve as active conduits for spatial propagation of cellular mechanotransduction through matrix exoskeleton, leading to efficient directed collective cell migration. Epithelial (MCF10A) cell clusters adhered to soft substrates with aligned collagen fibers (AF) migrate faster with much lesser traction forces, compared to random fibers (RF). Fiber alignment causes higher motility waves and transmission of normal stresses deeper into cell monolayer while minimizing shear stresses and increased cell-division based fluidization. By contrast, fiber randomization induces cellular jamming due to breakage in motility waves, disrupted transmission of normal stresses, and heightened shear driven flow. Using a novel motor-clutch model, we explain that such force-effective fast migration phenotype occurs due to rapid stabilization of contractile forces at the migrating front, enabled by higher frictional forces arising from simultaneous compressive loading of parallel fiber-substrate connections. We also model haptotaxis to show that increasing ligand connectivity (but not continuity) increases migration efficiency. According to our model, increased rate of front stabilization via higher resistance to substrate deformation is sufficient to capture durotaxis. Thus, our findings reveal a new paradigm wherein the rate of leading-edge stabilization determines the efficiency of supracellular collective cell migration.

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Bagchi, A., Sarker, B., Zhang, J., Foston, M., Pathak, A.. 2022-10-24. A fast yet force-effective mode of collective cell migration on aligned fibers due to rapid stabilization of contractile forces. https://doi.org/10.1101/2022.10.22.513348

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