Extracellular matrix

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Illustration depicting extracellular matrix (basement membrane and interstitial matrix) in relation to epithelium, endothelium and connective tissue

In biology, the extracellular matrix (ECM) is the extracellular part of animal tissue that usually provides structural support to the cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.

Extracellular matrix includes the interstitial matrix and the basement membrane.[1] Interstitial matrix is present between various cells (i.e., in the intercellular spaces) . Gels of polysaccharides and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM.[2] Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest.

Role and importance

Due to its diverse nature and composition, the ECM can serve many functions, such as providing support and anchorage for cells, segregating tissues from one another, and regulating intercellular communication. The ECM regulates a cell's dynamic behavior. In addition, it sequesters a wide range of cellular growth factors, and acts as a local depot for them.[1] Changes in physiological conditions can trigger protease activities that cause local release of such depots. This allows the rapid and local growth factor-mediated activation of cellular functions, without de novo synthesis.

Formation of the extracellular matrix is essential for processes like growth, wound healing and fibrosis. An understanding of ECM structure and composition also helps in comprehending the complex dynamics of tumor invasion and metastasis in cancer biology[1] as metastasis often involves the destruction of extracellular matrix[3] by enzymes such as serine and Threonine proteases and Matrix metalloproteinase.[1]

Molecular components

Components of the ECM are produced intracellularly by resident cells, and secreted into the ECM via exocytosis.[4] Once secreted they then aggregate with the existing matrix. The ECM is composed of an interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs).

Proteoglycan matrix components

GAGs are carbohydrate polymers and are usually attached to extracellular matix proteins to form proteoglycans (hyaluronic acid is a notable exception, see below). Proteoglycans have a net negative charge that attracts water molecules, keeping the ECM and resident cells hydrated. Proteoglycans may also help to trap and store growth factors within the ECM.

Described below are the different types of proteoglycan found within the extracellular matrix.

Heparan sulfate proteoglycans

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell suface or extracellular matrix proteins.[5][6] It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including developmental processes, angiogenesis, blood coagulation and tumour metastasis.

In the extracellular matrix, especially basement membranes, the multi-domain proteins perlecan, agrin and collagen XVIII are the main proteins to which heparan sulfate is attached.

Chondroitin sulfate proteoglycans

Chondroitin sulfates contribute to the tensile strength of cartilage, tendons, ligaments and walls of the aorta.

Keratan sulfate proteoglycans

Keratan sulfates have a variable sulfate content and unlike many other GAGs, does not contain uronic acid. It is present in the cornea, cartilage, bones and the horns of animals.

Non proteoglycan matrix components

Hyaluronic acid

Hyaluronic acid (or "hyaluronan") is a polysaccharide consisting of alternative residues of D-glucuronic acid and N-acetylglucosamine, and unlike other GAGs is not found as a proteoglycan. Hyaluronic acid in the extracellular space confers upon tissues the ability to resist compression by providing a counteracting turgor (swelling) force by absorbing alot of water. Hyaluronic acid is thus found in abundance in the ECM of load-bearing joints. It is also a chief component of the interstitial gel. Hyaluronic acid is found on the inner surface of the cell membrane and is translocated out of the cell during biosynthesis.[7]

Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflamation and tumor development. It interacts with a specific transmembrane receptor, CD44.[8]


Collagens are, in most animals, the most abundant glycoproteins in the ECM. In fact, collagen is the most abundant protein in the human body[9][10] and accounts for 90% of bone matrix protein content.[11] Collagens are present in the ECM as fibrillar proteins and give structural support to resident cells. Collagen is exocytosed in precursor form (procollagen), which is then cleaved by procollagen proteinases to allow extracellular assembly. Diseases such as osteogenesis imperfecta and epidermolysis bullosa are linked with genetic defects in collagen-encoding genes.[4]


Fibronectins are proteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Fibronectins bind collagen and cell surface integrins, causing a reorganization of the cell's cytoskeleton and facilitating cell movement. Fibronectins are secreted by cells in an unfolded, inactive form. Binding to integrins unfolds fibronectin molecules, allowing them to form dimers so that they can function properly. Fibronectins also help at the site of tissue injury by binding to platelets during blood clotting and facilitating cell movement to the affected area during wound healing.[4]


Elastins, in contrast to collagens, give elasticity to tissues, allowing them to stretch when needed and then return to their original state. This is useful in blood vessels, the lungs and in skin, and these organs contain high amounts of elastins. Elastins are synthesized by fibroblasts and smooth muscle cells. Elastins are highly insoluble, and tropoelastins are secreted inside a chaperone molecule, which releases the precursor molecule upon contact with a fiber of mature elastin. Tropoelastins are then deaminated to become incorporated into the elastin strand. Diseases such as cutis laxa and Williams syndrome are associated with deficient or absent elastin fibers in the ECM.[4]


Laminins are proteins found in the basal laminae of virtually all animals. Rather than forming collagen-like fibers, laminins form networks of web-like structures that resist tensile forces in the basal lamina. They also assist in cell adhesion. Laminins bind other ECM components such as collagens, nidogens, and entactins.[4]

Cell adhesion to the ECM

Many cells bind to components of the extracellular matrix. This cell-to-ECM adhesion is regulated by specific cell surface cellular adhesion molecules (CAM) known as integrins. Integrins are cell surface proteins that bind cells to ECM structures, such as fibronectin and laminin, and also to integrin proteins on the surface of other cells.

Fibronectins bind to ECM macromolecules and facilitate their binding to transmembrane integrins. The attachment of fibronectin to the extracellular domain initiates intracellular signaling pathways as well as association with the cellular cytoskeleton via a set of adaptor molecules such as actin.[2]

Cell types involved in ECM formation

There are many cell types that contribute to the development of the various types of extracellular matrix found in plethora of tissue types. The local components of ECM determine the properties of the connective tissue.

Fibroblasts are the most common cell type in connective tissue ECM, in which they synthesize, maintain and provide a structural framework; fibroblasts secrete the precursor components of the ECM, including the ground substance. Chondrocytes are found in cartilage and produce the cartilagenous matrix. Osteoblasts are responsible for bone formation.

Extracellular matrix in plants

Plant cells are tesselated to form tissues. The cell wall is the relatively rigid structure surrounding the plant cell. The cell wall provides lateral strength to resist osmotic turgor pressure, but is flexible enough to allow cell growth when needed; it also serves as a medium for intercellular communication. The cell wall comprises multiple laminate layers of cellulose microfibrils embedded in a matrix of glycoproteins such as hemicellulose, pectin, and extensin. The components of the glycoprotein matrix help cell walls of adjacent plant cells to bind to each other. The selective permeability of the cell wall is chiefly governed by pectins in the glycoprotein matrix. Plasmodesmata (singular: plasmodesma) are pores that traverse the cell walls of adjacent plant cells. These channels are tightly regulated and selectively allow molecules of specific sizes to pass between cells.[7]


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  2. 2.0 2.1 Alberts B, Bray D, Hopin K, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2004). "Tissues and Cancer". Essential cell biology. New York and London: Garland Science. ISBN 0-8153-3481-8.
  3. Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S (1980). "Metastatic potential correlates with enzymatic degradation of basement membrane collagen". Nature. 284 (5751): 67–8. PMID 6243750.
  4. 4.0 4.1 4.2 4.3 4.4 Plopper G (2007). The extracellular matrix and cell adhesion, in Cells (eds Lewin B, Cassimeris L, Lingappa V, Plopper G). Sudbury, MA: Jones and Bartlett. ISBN 0-7637-3905-7.
  5. Gallagher, J.T., Lyon, M. (2000). "Molecular structure of Heparan Sulfate and interactions with growth factors and morphogens". In Iozzo, M, V. Proteoglycans: structure, biology and molecular interactions. Marcel Dekker Inc. New York, New York. pp. 27–59.
  6. Iozzo, R. V. (1998). "Matrix proteoglycans: from molecular design to cellular function". Annu. Rev. Biochem. 67: 609–652. PMID 9759499.
  7. 7.0 7.1 Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. Molecular Cell Biology (5th ed.). New York: WH Freeman and Company. pp. 197–234. Unknown parameter |Chapter= ignored (|chapter= suggested) (help)
  8. Peach et al 1993. Identification of hyaluronic acid binding sites in the extracellular domain of CD44. The Journal of Cell Biology, Vol 122, 257-264
  9. Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San Antonio JD (2002). "Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen". J. Biol. Chem. 277 (6): 4223–31. doi:10.1074/jbc.M110709200. PMID 11704682.
  10. Karsenty G, Park RW (1995). "Regulation of type I collagen genes expression". Int. Rev. Immunol. 12 (2–4): 177–85. PMID 7650420.
  11. Kern B, Shen J, Starbuck M, Karsenty G (2001). "Cbfa1 contributes to the osteoblast-specific expression of type I collagen genes". J. Biol. Chem. 276 (10): 7101–7. doi:10.1074/jbc.M006215200. PMID 11106645.

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