Fibril Formation and Matrix Assembly

The single most important question with respect to the structure and function of fibronectin is the mechanism by which cells convert it from a relatively compact soluble protomer into an insoluble form that is visible by fluorescence microscopy as a fibrillar meshwork. This is a highly regulated process that utilizes integrins and possibly other cell-surface receptors [ref] including uPAR (urokinase-type plasminogen activator receptor) [ref] and a cell-surface proteoglycan [ref]. At the same time, those who work with purified Fn in solution are frequently frustrated by its tendency to form thread-like filamentous structures inadvertently upon agitation, contact with glass surfaces, extrusion through Hamilton syringes and other manipulations. This spontaneous process could make use of the same interaction sites as the one that is driven by cells. However nothing is known about the arrangement of individual molecules in these accidental fibrils. Electron microscopic analyses of natural thin fibrils (5-18nm diameter), made by fibroblasts in culture, clearly indicate an ordered arrangement and suggest a model in which extended protomers (130nm long) are arranged end-to-end with an overlap of about 14 nm [ref].