Multiscale relationships between fibronectin structure and functional properties.

Cell behavior is tightly coupled to the properties of the extracellular matrix (ECM) to which they attach. Fibronectin (Fn) forms a supermolecular, fibrillar component of the ECM that is prominent during development, wound healing and the progression of numerous diseases. This indicates that Fn has an important function in controlling cell behavior during dynamic events in vivo. The multiscale architecture of Fn molecules assembled into these fibers determines the ligand density of cell adhesion sites on the surface of the Fn fiber, Fn fiber porosity for cell signaling molecules such as growth factors, the mechanical stiffness of the Fn matrix and the adhesivity of Fn for its numerous soluble ligands. These parameters are altered by mechanical strain applied to the ECM. Recent efforts have attempted to link the molecular properties of Fn with bulk properties of Fn matrix fibers. Studies of isolated Fn fibers have helped to characterize the fiber's material properties and, in combination with models of Fn molecular behavior in the fibers, have begun to provide insights into the Fn molecular arrangement and intermolecular adhesions within the fibers. A review of these studies allows the development of an understanding of the mechanobiological functions of Fn.