Extracellular Matrix

Tissues are not made up solely of cells. A large part of their volume is made up of an extracellular matrix. This matrix is composed of a variety of proteins and polysaccharides (i.e., a molecule made up of many sugars). These proteins and polysaccharides are secreted locally and are organized into a supporting meshwork in close association with the cells that produced them. The amount and composition of the matrix vary with the different tissues and their function. In bone, for example, the matrix is more plen­tiful than the cells that surround it; in the brain, the cells are much more abundant, and the matrix is only a minor constituent.

Two main classes of extracellular macromolecules make up the extracellular matrix. The first is composed of polysaccharide chains of a class called glycosaminoglycans (GAGs), which are usually found linked to protein as pro-teoglycans. The second type consists of the fibrous pro­teins (i.e., collagen and elastin) and the fibrous adhesive proteins (i.e., fibronectin and laminin) that are found in the basement membrane. Members of each of these two classes of extracellular macromolecules come in a variety of shapes and sizes.

The proteoglycan and GAG molecules in connective tissue form a highly hydrated, gel-like substance, or tissue gel, in which the fibrous proteins are embedded. The poly­saccharide gel resists compressive forces, the collagen fibers strengthen and help organize the matrix, the rubber-like elastin adds resilience, and the adhesive proteins help cells attach to the appropriate part of the matrix. Polysaccha­rides in the tissue gel are highly hydrophilic, and they form gels even at low concentrations. They also accumulate a negative charge that attracts cations such as sodium, which are osmotically active, causing large amounts of water to be sucked into the matrix. This creates a swelling pressure, or turgor, that enables the matrix to withstand extensive compressive forces. This is in contrast to collagen, which

resists stretching forces. For example, the cartilage matrix that lines the knee joint can support pressures of hundreds of atmospheres by this mechanism.

Glycosaminoglycan and proteoglycan molecules in connective tissue usually constitute less than 10% by weight of fibrous tissue. Because they form a hydrated gel, the molecules fill most of the extracellular space, providing mechanical support to the tissues while ensuring rapid dif­fusion of water and electrolytes and the migration of cells. One GAG, hyaluronan or hyaluronic acid, is thought to play an important role as a space-filler during embryonic development. It creates a cell-free space into which cells subsequently migrate. When cell migration and organ de­velopment are complete, the excess hyaluronan is de­graded by the enzyme hyaluronidase. Hyaluronan is also important in directing the cell replacement that occurs during wound repair (see Chapter 20).

Three types of fibers are found in the extracellular space: collagen, elastin, and reticular fibers. Collagen is the most common protein in the body. It is a tough white fiber that serves as the structural framework for skin, liga­ments, tendons, and many other structures. Elastin acts like a rubber band; it can be stretched and then returns to its original form. Elastin fibers are abundant in structures sub­jected to frequent stretching, such as the aorta and some ligaments. Reticular fibers are extremely thin fibers that cre­ate a flexible network in organs subjected to changes in form or volume, such as the spleen, liver, uterus, or in­testinal muscle layer.