20. MODULE 20.pdf

MODULE 20 Extracellular Matrix (ECM) the non-cellular component in tissues and organs; mainly produced by local cells; in most connective tissues, ECM molecules are secreted by fibroblasts three classes of molecules: (1) glycosaminoglycans (GAGs), usually covalently linked to protein to form p...

MODULE 20 Extracellular Matrix (ECM) the non-cellular component in tissues and organs; mainly produced by local cells; in most connective tissues, ECM molecules are secreted by fibroblasts three classes of molecules: (1) glycosaminoglycans (GAGs), usually covalently linked to protein to form proteoglycans, (2) fibrous proteins (collagen, elastin), and (3) adhesive proteins ECM Functions gives tissues their identifiable properties: bone matrix - hardness, cartilage matrix - toughness and flexibility, tendon matrix - tensile strength, corneal stroma matrix - transparency provides strength, support, and protection to parts of the body “binds” cells together defines tissue architecture/organization; allows compartmentalization acts as a barrier (or filter) for macromolecules (e.g., basal lamina) determines cell shape, survival, development, migration, proliferation, and function Glycosaminoglycans (GAGs) stiff, hydrophilic, unbranched chains of disaccharide units the unit is an amino sugar (N-acetylglucosamine or N-acetylgalactosamine), frequently sulfated, and a second sugar, usually uronic acid the sulfate and carboxyl groups result in a negative charge form gels since the negative charges attract cations that retain water; the gel-like structures withstand compression four groups of GAGs: (1) hyaluronan, (2) chondroitin sulfate/dermatan sulfate, (3) heparan sulfate, (4) keratan sulfate The Glycosaminoglycan Hyaluronan a repeating sequence of ~25,000 non-sulfated disaccharide units usually not linked covalently to a protein synthesized at the cell surface, by an enzyme complex in the plasma membrane resists compressive forces in embryogenesis, provides a space filler that shapes structures and provides space, into which cells migrate MODULE 20 Proteoglycans except for hyaluronan, other GAGs are covalently attached to proteins to form proteoglycans the polysaccharide chains are mainly added to a core protein in the Golgi, and some sugars are covalently modified proteoglycans form a hydrated gel, in which fibrous proteins are embedded the gel resists compressive forces and permits the diffusion of nutrients/metabolites and hormones between the blood and cells Proteoglycans articular cartilage: the tissue at the ends of bones, where they form joints; healthy cartilage allows the bones to glide over each other with little friction cartilage: ECM of collagen and elastic fibers in a gel of GAGs and proteoglycans the negatively charged proteoglycans have a high affinity for water functions: absorption, distribution of compressive weight, protection of structures in the joints from mechanical damage Glucosamine as Therapy for Osteoarthritis osteoarthritis: a form of joint disease, that leads to pain and physical disability glucosamine is an aminosaccharide, a substrate for the synthesis of GAGs and, therefore, for the production of proteoglycans in cartilage chondroitin sulfate is a sulfated glycosaminoglycan usually found attached to proteins as part of a proteoglycan glucosamine and chondroitin sulfate, over-the-counter dietary supplements in the U.S., have effects in relieving pain and stopping the progression of osteoarthritis Putting It Together a substantial portion of the tissue volume is filled by ECM ECM binds cells, influences their survival, development, shape, polarity, and behavior ECM contains proteoglycans, fibrous proteins, and adhesive proteins proteoglycans are composed of glycosaminoglycans and proteins; proteoglycans provide resilience and resistance to compressive forces GAGs are negatively charged polysaccharides except for hyaluronan, GAGs are covalently linked to proteins to form proteoglycans proteoglycans form hydrated gels and can function as cell surface co-receptors