1. Fast yet force-effective mode of supracellular collective cell migration due to extracellular force transmission.
- Author
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Bagchi, Amrit, Sarker, Bapi, Zhang, Jialiang, Foston, Marcus, and Pathak, Amit
- Subjects
MECHANOTRANSDUCTION (Cytology) ,FRICTION ,SHEAR flow ,COMPRESSION loads ,CELL migration - 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. Author summary: Cellular forces are critical for their collective migration on matrices of various stiffness and topographies. While migrating cells can align collagen fibers, it remains unknown whether such force requirement changes with pre-aligned fibers. On soft surfaces with aligned collagen fibers, we discovered a new mode of fast collective cell migration that requires drastically lower traction forces, compared to surfaces without aligned fibers. Through traction force and monolayer stress microscopy calculations and a new motor-clutch model, we further discovered that this novel mode of "fast and force-effective" collective cell migration is achieved by rapid stabilization of cellular contractile forces via simultaneous engagement of fiber-substrate linkages when cells pull on aligned fibers. This phenomenon results in higher fluidization and stress relaxation within the monolayer, allowing the monolayer to expand freely. Although high traction forces have conventionally been associated with fast cell migration, our findings show that aligned fibers relax that force requirement via fast contractility stabilization. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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