Editing Fibronectin (section)

== Matrix assembly ==
[[Cell (biology)|Cellular]] fibronectin is assembled into an [[insoluble]] [[fibrillar]] [[extracellular matrix|matrix]] in a complex cell-mediated process.<ref name="pmid12857786">{{cite journal | vauthors = Wierzbicka-Patynowski I, Schwarzbauer JE | title = The ins and outs of fibronectin matrix assembly | journal = Journal of Cell Science | volume = 116 | issue = Pt 16 | pages = 3269–76 | date = Aug 2003 | pmid = 12857786 | doi = 10.1242/jcs.00670 | s2cid = 16975447 | doi-access =  }}</ref>  Fibronectin matrix assembly begins when soluble, compact fibronectin [[protein dimer|dimers]] are [[secreted]] from cells, often [[fibroblasts]].  These soluble dimers bind to [[α5β1]] [[integrin]] receptors on the cell surface and aid in clustering the integrins.  The local [[concentration]] of integrin-bound fibronectin increases, allowing bound fibronectin [[macromolecule|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 cryptic fibronectin-binding sites are exposed along the length of a bound fibronectin molecule. Cells are believed to stretch fibronectin by pulling on their fibronectin-bound integrin receptors. This [[force]] partially unfolds the fibronectin [[ligand (biochemistry)|ligand]], unmasking cryptic fibronectin-binding sites 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 [[extracellular matrix|matrix]].

A transmembrane protein, [[CD93]], has been shown to be essential for fibronectin matrix assembly (fibrillogenesis) in human dermal blood endothelial cells.<ref name="Lugano_2018">{{cite journal | vauthors = Lugano R, Vemuri K, Yu D, Bergqvist M, Smits A, Essand M, Johansson S, Dejana E, Dimberg A | title = CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis | journal = The Journal of Clinical Investigation | volume = 128 | issue = 8 | pages = 3280–3297 | date = August 2018 | pmid = 29763414 | pmc = 6063507 | doi = 10.1172/JCI97459 }}</ref> As a consequence, knockdown of CD93 in these cells resulted in the disruption of the fibronectin fibrillogenesis. Moreover, the CD93 knockout mice retinas displayed disrupted fibronectin matrix at the retinal sprouting front.<ref name="Lugano_2018" />