Ground substance

Ground substance

Ground substance is found in all cavities and clefts between the fibres and cells of connective tissues. Water, salts and other low molecular substances are contained within the ground substance, but its main structural constituent are proteoglycans.
Ground substance is soluble in most of the solvents used to prepare histological sections and therefore not visible in ordinary sections.

Proteoglycans are responsible for the highly viscous character of the ground substance. Proteoglycans consist of proteins (~5%) and polysaccharide chains (~95%), which are covalently linked to each other. The polysaccharide chains belong to one of the five types of glycosaminoglycans, which form the bulk of the polysaccharides in the ground substance.

Hyaluronan(or hyaluronic acid) is the dominant glycosaminoglycan in connective tissues. The molecular weight (MW) of hyaluronic acid is very high (~ MW 1,000,000 ). With a length of about 2.5 µm hyaluronan is very large. Hyaluronan serves as a "backbone" for the assembly of other glycosaminoglycans in connective and skeletal tissue, which results in even larger molecule complexes (MW 30,000,000 - 200,000,000).
Hyaluronan is also a major component of the synovial fluid, which fills joint cavities, and the vitreous body of the eye.

The remaining four major glycosaminoglycans are chondroitin sulfate, dermatan sulfate, keratan sulfate and heparan sulfate. These glycosaminoglycans attach via core- and link-proteins to a backbone formed by the hyaluronic acid. The coiled arrangement of the hyaluronan and other attached glucosaminoglycans fills a roughly spherical space with a diameter of ~0.5 µm. This space is called a domain. Neighbouring domains overlap and form a more or less continuous three-dimensional molecular sievein the interstitial spaces of the connective tissues.

The large polyanionic carbohydrates of the glycosaminoglycans bind large amounts of water and cations. The bound water in the domains forms a medium for the diffusion of substances of low molecular weight such as gases, ions and small molecules, which can take the shortest route, for example, from capillaries to connective tissue cells. Large molecules are excluded from the domains and have to find their way through the spaces between domains.

The restricted motility of larger molecules in the extracellular space inhibits the spread of microorganisms through the extracellular space. A typical bacterium ( 0.5 x 1 µm) is essentially immobilised in the meshwork formed by the domains. The pathogenicity of a bacterium is indeed to some extent determined by its ability to find its way through the mesh, and some of the more invasive types produce the enzyme hyaluronidase, which depolymerises hyaluronic acid.

The components of the ground substance, collagen, elastic and reticular fibres are synthesised by cells of the connective tissues, the fibrocytes.