Fibronectin can exist both in a soluble form, circulating in the blood and other body fluids, and as insoluble fibronectin fibrils, in which fibronectin dimers are cross-linked to one another by additional disulfide bonds and form part of the extracellular matrix. Unlike fibrillar collagen molecules, however, which can self-assemble into fibrils in a test tube, fibronectin molecules assemble into fibrils only on the surface of cells, and only where those cells possess appropriate fibronectin-binding proteins—in particular, integrins. The integrins provide a linkage from the fibronectin outside the cell to the actin cytoskeleton inside it. The linkage transmits tension to the fibronectin molecules—provided that they also have an attachment to some other structure—and stretches them, exposing cryptic binding sites in the fibronectin molecules (Figure 19–48). This allows them to bind directly to one another and to recruit additional fibronectin molecules to form a fibril (Figure 19–49). This dependence on tension and interaction with cell surfaces ensures that fibronectin fibrils assemble where there is a mechanical need for them and not in inappropriate locations such as the bloodstream.
Many other extracellular matrix proteins contain multiple copies of the type III fibronectin repeat (see Figure 19–46), and it is possible that tension exerted on these proteins also uncovers cryptic binding sites and thereby influences their behavior.
the Basal Lamina Is a Specialized Form of Extracellular Matrix
Thus far in this section we have reviewed the general principles underlying the structure and function of the major classes of extracellular matrix components. We now describe how some of these components are assembled into a specialized type of extracellular matrix called the basal lamina (also known as the basement membrane). This exceedingly thin, tough, flexible sheet of matrix molecules is an essential underpinning of all epithelia. Although small in volume, it has a critical role in the architecture of the body. Like the cadherins, it seems to be one of the defining features common to all multicellular animals, and it seems to have appeared very early in their evolution. The major molecular components of the basal lamina are among the most ancient extracellular matrix macromolecules.
Basal laminae are typically 40–120 nm thick. A sheet of basal lamina not only lies beneath epithelial cells but also surrounds individual muscle cells, fat cells,
Figure 19–48 Tension-sensing by fibronectin. Some type III fibronectin repeats are thought to unfold when fibronectin is stretched. the unfolding exposes cryptic binding sites that interact with other fibronectin molecules resulting in the formation of fibronectin filaments like those shown in Figure 19–49. (From
V. Vogel and M. Sheetz, Nat. Rev. Mol. Cell Biol. 7:265–275, 2006. With permission from Macmillan publishers Ltd.)