Fibronectin fibrillogenesis facilitates mechano-dependent cell spreading, force generation, and nuclear size in XXXX embryonic fibroblasts.

@entity1 @entity11504
UNASSIGNED: Cells respond to mechanical cues from the substrate to which they are attached. These mechanical cues drive cell migration, proliferation, differentiation, and survival. Previous studies have highlighted three specific mechanisms through which substrate stiffness directly alters cell function: increasing stiffness drives (1) larger contractile forces; (2) increased cell spreading and size; and (3) altered nuclear deformation. While studies have shown that substrate mechanics are an important cue, the role of the extracellular matrix (ECM) has largely been ignored. The ECM is a crucial component of the mechanosensing system for two reasons: (1) many ECM fibrils are assembled by application of cell-generated forces, and (2) ECM proteins have unique mechanical properties that will undoubtedly alter the local stiffness sensed by a cell. We specifically focused on the role of the ECM protein @entity11504 ( @entity11504 ), which plays a critical role in de novo tissue production. In this study, we first measured the effects of substrate stiffness on @entity1 embryonic fibroblasts by plating cells onto microfabricated pillar arrays (MPAs) of varying stiffness. Cells responded to increasing substrate stiffness by generating larger forces, spreading to larger sizes, and altering nuclear geometry. These cells also assembled @entity11504 fibrils across all stiffnesses, with optimal assembly occurring at approximately 6 kPa. We then inhibited @entity11504 assembly, which resulted in dramatic reductions in contractile force generation, cell spreading, and nuclear geometry across all stiffnesses. These findings suggest that @entity11504 fibrils play a critical role in facilitating cellular responses to substrate stiffness.
