3D mesenchymal cell migration is driven by anterior cellular contraction that generates an extracellular matrix prestrain

We describe a cellular contractile mechanism employed by fibroblasts and mesenchymal cancer cells to migrate in 3D collagen gels. During 3D spreading, fibroblasts strongly deform the matrix. They protrude, polarize, and initiate migration in the direction of highest extracellular matrix (ECM) deformation (prestrain). This prestrain is maintained through anterior cellular contractions behind the leading edge prior to protrusion, coordinating a distinct 3D migration cycle that varies between cell types. Myosin IIA is required for strain polarization, generating anterior contractions, and maintaining prestrain for efficient directional cell migration. Local matrix severing disrupts the matrix prestrain, suppressing directional protrusion. We show that epithelial cancer and endothelial cells rarely demonstrate the sustained prestrain or anterior contractions. We propose that mesenchymal cells sense ECM stiffness in 3D and generate their own matrix prestrain. This requires myosin IIA to generate polarized periodic anterior contractions for maintaining a 3D migration cycle.

Automated summary

The study reveals that fibroblasts and mesenchymal cancer cells utilize a cellular contractile mechanism to migrate in 3D collagen gels, with varying 3D migration cycles between cell types. It is essential for efficient directional cell migration to maintain prestrain and anterior contractions, which require myosin IIA. Epithelial cancer and endothelial cells show little sustained prestrain or anterior contractions, suggesting a different mechanism for migration.