The extracellular matrix
This is the first update. Much more will follow
In a lot of the connective tissues, the extracellular matrix molecules are secreted by cells called fibroblasts. These molecules assemble into the extracellular matrix once they are secreted.
The extracellular matrix is made up of two classes of macromolecules. The first class is called glycosaminoglycans, which are polysaccharide chains. Members of this class are usually found to be covalently linked to protein in the form of proteoglycans. The second class is made up by fibrous proteins. There are two functional types of fibrous proteins: the ones that are mainly structural, like collagen and elastin for example, and the ones that are mainly adhesive, like fibronectin and laminin for example. Members of both classes come in a great variety of shapes and sizes.
The members of the glycosaminoglycans form a highly hydrated, gel-like substance, in which the members of the fibrous proteins are embedded. Collagen fibers strengthen and help to organize the matrix, while elastin fibres give it resiliance. The adhesive proteins help cells to attach to the extracellular matrix. Fibronectin for example promotes the attachment of fibroblasts and other cells to the matrix in connective tissues via the extracellular parts of some members of the integrin family, while laminin promotes the attachment of epithelial cells to the basal lamina, again via the extracellular domains of some members of integrins.
Collagen
The collagens are a family of fibrous proteins found in all multicellular animals. Characteristic about these collagens is their long, stiff, helical structure. Three collagen polypeptide chains, which are called alpha chains are wound around each other to form a superhelix. After collagens are secreted in the form of propeptides, they are converted to collagen molecules by specific proteolytic enzymes which reside outside the cells. The collagens then assemble in the extracellular space to form collagen fibres which are much larger than the single molecules. These basic structures organize the extracellular matrix and give it resiliance.
The part described above is true for the volume filling material between cells, but beneath epithelia the extracellular matrix is organized as a thin sheet called the basal lamina (40-120 nm thick). The construction of this lamina depends on a specialized variety of collagen called type IV collagen. Molecules of this type of collagen have a more flexible structure then their fibrilar counterparts. They form a flexible, sheetlike multilayered network.
Fibronectin
Fibronectin was the first well characterized adhesive protein. It's build up of multiple domains, each with specific binding sites for other matrix macromolecules and for receptors on the surfaces of cells. Fibronectin is a large glycoprotein that is found in all vertebrates. It exists as a dimer composed of two very lagre subunits joined by a pair of disulfide bonds near their carboxyl termini. Each subunit is folded into a series of functionally distinct domains separated by regions of flexible polypeptide chain. In experiments with chopped up fibronectin molecules it was shown that one domain binds to collagen, another to heparin, and yet another to specific integrins on the surfaces of various types of cells. From such domains with cell-binding activity, synthetic peptides corresponding to different segments of these domains were made to determine which region was responsible for the binding. From these experiments a tripeptide sequence was found which could compete with fibronectin for the binding site on cells. This RGD sequence (short for the amino acids Arg-Gly-Asp) can when coupled to a surface cause cells to adhere to it.
Last updated on 03/02/97
© 1997 jkoster@hotmail.com
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