Measuring the biomechanical properties of cell-derived fibronectin fibrils

Embryonic development, wound healing, and organogenesis all require assembly of the extracellular matrix protein fibronectin (FN) into insoluble, viscoelastic fibrils. FN fibrils mediate cell migration, force generation, angiogenic sprouting, and collagen deposition. While the critical role of FN fibrils has long been appreciated, we still have an extremely poor understanding of their mechanical properties and how these mechanical properties facilitate cellular responses. Here, we demonstrate the development of a system to probe the mechanics of cell-derived FN fibrils and present quantified mechanical properties of these fibrils. We demonstrate that: fibril elasticity can be classified into three phenotypes: linearly elastic, strain-hardening, or nonlinear with a "toe" region; fibrils exhibit pre-conditioning, with nonlinear "toe" fibrils becoming more linear with repeated stretch and strain-hardened fibrils becoming less linear with repeated stretch; fibrils exhibit an average elastic modulus of roughly 8 MPa; and fibrils exhibit a time-dependent viscoelastic behavior, exhibiting a transition from a stress relaxation response to an inverse stress relaxation response. These findings have a potentially significant impact on our understanding of cellular mechanical responses in fibrotic diseases and embryonic development, where FN fibrils play a major role.