the Extracellular Matrix Is Made and Oriented by the Cells Within It
The macromolecules that constitute the extracellular matrix are mainly produced locally by cells in the matrix. As we discuss later, these cells also help to organize the matrix: the orientation of the cytoskeleton inside the cell can control the orientation of the matrix produced outside. In most connective tissues, the matrix macromolecules are secreted by cells called fibroblasts (Figure 19–30). In certain specialized types of connective tissues, such as cartilage and bone, however, they are secreted by cells of the fibroblast family that have more specific names: chondroblasts, for example, form cartilage, and osteoblasts form bone.
The extracellular matrix is constructed from three major classes of macromolecules: (1) glycosaminoglycans (GAGs), which are large and highly charged polysaccharides that are usually covalently linked to protein in the form of proteoglycans; (2) fibrous proteins, which are primarily members of the collagen family; and (3) a large class of noncollagen glycoproteins, which carry conventional asparagine-linked oligosaccharides (described in Chapter 12). All three classes of macromolecule have many members and come in a great variety of shapes and
Figure 19–30 Fibroblasts in connective tissue. this scanning electron micrograph shows tissue from the cornea of a rat. the extracellular matrix surrounding the fibroblasts is here composed largely of collagen fibrils. the glycoproteins, hyaluronan, and proteoglycans, which normally form a hydrated gel filling the interstices of the fibrous network, have been removed by enzyme and acid treatment. (Courtesy of t. Nishida.) sizes (Figure 19–31). Mammals are thought to have almost 300 matrix proteins, including about 36 proteoglycans, about 40 collagens, and over 200 glycoproteins, which usually contain multiple subdomains and self-associate to form multimers. Add to this the large number of matrix-associated proteins and enzymes that can modify matrix behavior by cross-linking, degradation, or other mechanisms, and one begins to see that the matrix is an almost infinitely variable material. Each tissue contains its own unique blend of matrix components, resulting in an extracellular matrix that is specialized for the needs of that tissue.
The proteoglycan molecules in connective tissue typically form a highly hydrated, gel-like “ground substance” in which collagens and glycoproteins are embedded. The polysaccharide gel resists compressive forces on the matrix while permitting the rapid diffusion of nutrients, metabolites, and hormones between the blood and the tissue cells. The collagen fibers strengthen and help organize the matrix, while other fibrous proteins, such as the rubberlike elastin, give it resilience. Finally, the many matrix glycoproteins help cells migrate, settle, and differentiate in the appropriate locations.
Glycosaminoglycan (GaG) Chains Occupy Large amounts of Space and Form hydrated Gels
Glycosaminoglycans (GAGs) are unbranched polysaccharide chains composed of repeating disaccharide units. One of the two sugars in the repeating disaccharide is always an amino sugar (N-acetylglucosamine or N-acetylgalactosamine), which in most cases is sulfated. The second sugar is usually a uronic acid (glucuronic or iduronic). Because there are sulfate or carboxyl groups on most of their sugars, GAGs are highly negatively charged (Figure 19–32). Indeed, they are the most anionic molecules produced by animal cells. Four main groups of GAGs are distinguished by their sugars, the type of linkage between the sugars, and the number and location of sulfate groups: (1) hyaluronan, (2) chondroitin sulfate and dermatan sulfate, (3) heparan sulfate, and (4) keratan sulfate.