(725g) Cell Motility and Traction Force Generation in Three-Dimensional Fibrin Hydrogels

The ability of cells to exert force on their surroundings underlies cell migration and extracellular matrix (ECM) remodeling, and is thus an essential aspect of complex, metazoan life. Due to technical challenges, few studies have examined how living cells transduce cytoskeletal force to the ECM in soft, three-dimensional (3D) environments. We used timelapse 3D imaging, quantitative image analysis, and theory to determine how fibroblasts embedded in a 3D fibrin matrix exert force on the surrounding ECM. Under these circumstances, cytoskeletal force generation and transmission are dominated by contractile actin bundles (stress fibers) attached at their ends to large, stable integrin-based adhesions (focal adhesions). Stress fiber contraction is counterbalanced by continuous elongation at focal adhesions. The resulting dynamic equilibrium can explain how cells maintain stable, contractile connections to the ECM during cell migration, and provides a probable means by which fibroblasts contract provisional matrices during wound healing.