Fibronectin is a glycoprotein of the extracellular matrix that binds to extracellular matrix components such as collagen, fibrin, heparan sulfate proteoglycans (e.g. syndecans) and membrane-spanning receptor proteins called integrins. Fibronectin exists as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds. There are two forms of fibronectin – the soluble and insoluble form. Soluble form of fibronectin is a plasma protein. Insoluble cellular fibronectin is a major component of the extracellular matrix called ECM fibronectin. It is secreted by various cells, primarily fibroblasts, as a soluble protein dimer and is then assembled into an insoluble matrix in a complex cell-mediated process. Fibronectin plays a major role in cell adhesion, growth, migration, differentiation, wound healing and matrix assembly. Altered fibronectin expression, degradation, and organization has been associated with a number of diseases. In the skin, fibronectin can function as a general cell adhesion molecule by anchoring cells to collagen or proteoglycan. FN also can organize cellular interaction with the ECM by binding to different components of the extracellular matrix and to membrane-bound FN receptors (i.e. the adhesion molecule integrin) on cell surfaces . There are three functional domains in fibronectin termed as FN type I, II, III. Twelve type I modules make up the amino-terminal and carboxyl-terminal region of the molecule, and are involved mainly in collagen and fibrin binding. Collagen binding site is FN type I_6–9. Only two type II modules are found in FN. They are instrumental in binding collagen. The most abundant module in fibronectin is Type III, which contains the RGD (integrin binding tripeptide) FN receptor recognition sequence along with binding sites for other integrins and heparin. There are four fibronectin-binding domains, allowing fibronectin to associate with other fibronectin molecules one of which is called assembly domain located at FN type I₅, and is required for the initiation of fibronectin matrix assembly.

ECM Fibronectin is assembled into an insoluble fibrillar matrix in a complex cell-mediated process. Fibronectin matrix assembly begins when soluble, compact fibronectin dimers that are secreted from cells, often fibroblasts. These soluble dimers bind to integrin receptors on the cell surface and the clustering of the integrins occur next. The local concentration of integrin-bound fibronectin thereby increases, allowing bound fibronectin molecules to more readily interact with one another. Short fibronectin fibrils then begin to form between adjacent cells. As matrix assembly proceeds, the soluble fibrils are converted into larger insoluble fibrils that comprise the extracellular matrix. Fibronectin’s shift from soluble to insoluble fibrils proceeds when fibronectin-binding domains are exposed along the length of a bound fibronectin molecules. Cells are believed to stretch fibronectin by pulling on their fibronectin-bound integrin receptors. This force partially unfolds the fibronectin-binding domain and allowing nearby fibronectin molecules to associate. This fibronectin-fibronectin interaction enables the soluble, cell-associated fibrils to branch and stabilize into an insoluble fibronectin matrix. fibronectin-binding domain (fibrillogenesis) is a critical regulator of extracellular matrix organization and stability. Fibronectin matrix assembly is also involved in the healing mechanism in response to tissue injury.

The age-related changes in fibronectin synthesis and degradation in human fibroblasts were studied in vitro. The amount of cell surface fibronectin and released fibronectin (extracellular fibronectin) in early and late passaged (senescent) human skin fibroblasts were measured. Cell surface fibronectin decreased dramatically in senescent fibroblast in vitro. A progressive increase in the rate of fibronectin synthesis per cell was observed by late passaged (senescent) human fibroblasts with no difference in the turnover of fibronectin, suggesting the rate of synthesis and degradation of fibronectin are both increased in senescent fibroblast in vitro. The increased fibronectin synthesis in senescent fibroblasts appeared to correlate with the general increase in rate of protein synthesis/cell. There are age-related defect in the biological activity of human fibroblast fibronectin regarding its activity in Interaction with collagen and in mediating cell-ECM component adhesion . In comparison to fibronectin isolated from early-passage cells, fibronectin from late-passage cells (in vitro aged) bound poorly to native collagen types I and II. This defective binding to native collagen may account for some aspects of the aged skin phenotype. There are reduced cell-ECM adhesion in aged fibroblast and this decreased cell-ECM component adhesion was due to a defect in fibronectin. Analysis of fibronectins purified from early and late passage (aged) fibroblast indicates that there are striking differences in their abilities to promote cell adhesion. In addition, normal fibroblast morphology were changed in the presence of the fibronectin isolated from aged cell. This defective cell-matrix adhesion function may also account for the overall stability and strength of the ECM in the skin. However, there seems no direct evidence linking the defective fibronectin or fibronectin fibrillogenesis on or released from the aged fibroblast to the clinical manifestations of an aging skin appearance such as wrinkles and skin laxity.

There are some anti-wrinkle ingredients that are claimed to be able to stimulate the production of fibronectin (and collagen) such as the widely used peptide ingredient Matrixyl 3000. ChroNOline™ is an commercial anti-wrinkle ingredient with proven clinical efficacy developed by Atrium that are able to boost the production of key components of the dermal-epidermal junction -collagen VII, laminin-5, and fibronectin. ChroNOline™ can induce/increase fibronectin production by 60% compared to the cells without adding ChroNOline™ in an in vitro assay and thus firmly anchors cells to the matrix for optimal cell functions. Deliner™ is a corn extract that smoothes out wrinkles by activating healing mechanisms in the skin. Deliner™ reduces the depth of wrinkles and smoothes the skin by its specific action on fibronectin and its activation of cell migration and multiplication.