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

Abstract

AbstractCell collectives use aligned extracellular matrix fibers for directed migration in development, regeneration, and cancer metastasis. However, it remains unknown whether fibers serve as active conduits for spatial propagation of cellular mechanotransduction leading to directed collective cell migration. In this work, we developed soft hydrogels coated with magnetically aligned collagen fibers and studied migration of defined epithelial clusters. We report that epithelial (MCF10A) cell clusters adhered to soft substrates with aligned collagen fibers (AF) migrate faster with much lesser traction forces, compared to those on uniform fibers (UF). Fiber alignment causes motility and force transmission deeper into the monolayer, leading to polarized cell flocking, compared to migration on UF where cellular jamming occurs. Using a motor-clutch model, we explain that force-effective fast migration phenotype occurs due to faster stabilization of cellular contractile forces enabled by aligned ligand connectivity. As a result, cells migrate faster with lesser effort, thereby revealing that aligned matrix topographies may help conserve energy for cell migration in fundamental biological processes such as wound repair and tumor invasion.Significance statementCellular forces are critical for their collective migration on matrices of various stiffness and topographies. While cells can align collagen fibers during migration, 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 monolayer stress microscopy calculations and a 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. Although high traction forces have conventionally been associated with fast cell migration, our findings show that aligned fibers relax that force requirement via contractility stabilization.