Living tissues are not just tight accumulations of cells.
Much of the volume of tissue is made up of extracellular space. This void is filled with a complex mesh called the extracellular matrix.
The extracellular matrix is a dynamic and physiologically active component of all living tissue rather than inert filler material, such as Styrofoam padding around a shipment of brittle material.
In addition to providing structural support for cells embedded within a tissue, the extracellular matrix guides tissue division, growth, and development.
In other words, the extracellular matrix largely determines how a tissue looks and functions.
The composition of the extracellular matrix is tissue-specific; however, its functions concerning cell adhesion, communication, and differentiation remain uniform regardless of the change in design.
The extracellular matrix acts as an adhesive that holds all tissue cells in place.
It also forms specialized structures, such as cartilage, tendons, and the basement membrane (also called the basal lamina).
It functions as a physical scaffold; it also provides a channel for cell migration and communication through signaling molecules.
It consists of various growth and differentiation factors that regulate and influence the development, migration, proliferation, shape, and metabolic functions of cells.
Production of the extracellular matrix
The extracellular matrix components are produced and organized by the cells that live within them.
In most tissues, fibroblasts or fiber-producing cells are responsible for carrying out this critical function.
In no tissue is the extracellular matrix so well defined or easily studied, as in connective tissue, where the extracellular matrix is often more abundant than cells.
Found throughout the entire body, connective tissue serves as the scaffold for all other tissues.
Variations in the types and numbers of molecules in the extracellular matrix of connective tissue explain the incredible diversity of tissues and organs in the human body.
A vivid example of how the extracellular matrix influences tissue function can be seen in the differences between the bones and the eye’s cornea.
In bone, the extracellular matrix is thick and highly mineralized, providing hard, inflexible, and opaque tissue – just what is needed to build a skeleton.
On the contrary, the extracellular matrix of the cornea consists of a flexible, transparent gel with high water content, ideal for transmitting light to the eyeball.
Structure of the extracellular matrix
The extracellular matrix comprises proteoglycans, water, minerals, and fibrous proteins.
A proteoglycan comprises a protein core surrounded by long chains of starch-like molecules called glycosaminoglycans.
The various components of the extracellular matrix make it exist as a highly organized structure.
Cells embedded in it interact with the matrix and with other cells due to the presence of specialized matrix receptor molecules.
These molecules interact with the matrix and the internal processes of the cell, which causes the cellular exchange of signals.
Despite the organized nature of this matrix, it is not rigid and static. It can be remodeled by a cell around itself, according to the requirements of that cell.
This remodeling occurs by the selective secretion of the extracellular matrix together with the action of proteolytic enzymes.
Since the composition of the extracellular matrix depends on the cells that secrete it, different organisms present essential differences concerning the extracellular matrix.
In the case of fungal organisms, the extracellular matrix is mainly composed of chitin. This is also true of invertebrates such as arthropods.
Plants have an extracellular matrix that is rich in cellulose. However, the most complex form of the extracellular matrix is possessed by multicellular vertebrates.
The extracellular matrix invertebrates
There are two primary components of the extracellular matrix, namely: the fibers and the ground substance.
Fibers are again divided into two functional categories: structural fibers and adhesive fibers.
The ground substance consists mainly of glycosaminoglycans, proteoglycans, and adhesive glycoproteins.
It is also composed of varying amounts of interstitial fluid called extracellular fluid.
They are long, rigid, and unbranched polysaccharide chains. These chains are composed of repeating disaccharide units, one of which is an amino sugar.
Amino sugars are mainly sulfated and possess carboxyl groups. Since these functional groups have a natural negative charge, they attract positive ions like sodium ions.
This quality allows the accumulation of a high sodium concentration in the base substance.
The high salt concentration due to the osmotic pressure leads to the migration of the interstitial fluid to the base substance.
The presence of this fluid imparts incompressibility, but at the same time, due to the negative charges on the glycosaminoglycans, the chains repel each other, eventually resulting in a slippery fluid (called mucus or synovial fluid).
Of the five main glycosaminoglycans, only one is not sulfated. The different types of glycosaminoglycans are as follows.
It is the only non-sulfated glycosaminoglycan and therefore does not bind to proteins to form proteoglycans.
It is widely distributed throughout the animal’s body and is found in varying amounts in almost all tissues and fluids in adults.
It can be seen in loose connective tissue, cartilage, skin, and vitreous and synovial fluid. It is a polysaccharide consisting of alternating units of D-glucuronic acid and N-acetylglucosamine.
Its presence makes the tissue resistant to compression, and therefore it is found in the load-bearing joints. It also acts as a regulatory molecule involved in healing, inflammation, and tumor development.
It has also been shown to interact with the CD44 transmembrane receptor to facilitate cell migration during tissue repair and morphogenesis.
It is mainly found in hyaline and elastic cartilage and bone tissues. Its chain consists of alternating units of N-acetylgalactosamine and glucuronic acid.
Provides tensile and mechanical strength to cartilage, aortic walls, ligaments, tendons, and bones.
They have also been observed to form large aggregates by binding to hyaluronic acid.
It is also known as chondroitin B sulfate and is mainly found in dermal tissues, tendons, ligaments, heart valves, fibrocartilage, arteries, and nerves.
It also consists of alternating units of N-acetylgalactosamine and glucuronic acid.
It binds to Type I collagen fibers to exhibit a role in coagulation, wound repair, and fibrosis.
It is found in bone, cartilage, and cornea. It is a linear polysaccharide consisting of alternating repeats of galactose and N-acetylgalactosamine.
It acts as a lubricating shock absorber and is therefore present in the joints; it also provides mechanical resistance to the tissues.
It consists of repeating units of glucuronic acid and N-acetylglucosamine and is found on the surface of fibroblasts and epithelial cells.
It is also found in the basal and external laminae. It’s binding to fibroblast growth factor allows it to mediate cell adhesion.
Its other function includes the regulation of angiogenesis, coagulation, and tumor metastasis.
They are the macromolecules formed due to the covalent bond between glycosaminoglycans and protein nuclei.
Glycosaminoglycans appear like the bristles of a bottle brush, with the wire stem represented by the protein core.
These macromolecules exhibit a high degree of viscosity and therefore act as good lubricating agents.
This also allows them to resist compression, and the dense nature prevents the rapid migration of microbes and metastatic cells.
Proteoglycans also possess specific binding sites for signaling molecules that, when bound, show an enhancement or impairment in their activity.
This binding capacity is also used to trap and store growth factors within the extracellular matrix.
They are separated into two categories according to their locations, and they are as follows.
They promote and improve cell adhesion. They are composed of two subtypes depending on the glycosaminoglycans attached.
- Aggrecan: consists of a protein core bound to keratan sulfate and chondroitin sulfate and is expressed in cartilage.
- Perlecan: The nature of the protein binds to heparan sulfate and is represented by all cells that comprise the basement membrane.
They are responsible for binding cells to fibronectin and collagen fibers.
- Syndecan: consists of heparan sulfate and chondroitin sulfate and is expressed by embryonic epithelial tissues, as well as fibroblasts and plasma cells.
They consist of several domains that bind individually to the cell surface and transmembrane integrins, collagen fibers, and proteoglycans.
This multiple binding helps regulate the ability of cells to adhere to the extracellular matrix.
In addition to their adhesive quality, they also function in transporting and transmitting signaling molecules between cells to cause tissue repair and development.
Entactin / Nidogen
It is present in the basement lamina and has a primary function of binding laminin with collagen fibers.
It is found mainly in the bones, where it promotes the adhesion of osteoblasts to the extracellular matrix, providing mechanical and tensile strength to the entire bone.
It is a particular glycoprotein expressed only in embryonic tissues, wounds, and tumors.
It plays a vital role in cell and tissue development and binds to cells through integrin molecules.
It is present in blood plasma, platelets, fibroblasts, endothelium, and smooth muscle cells.
In the case of tissue damage or injury, it is secreted by blood platelets and binds to fibrinogen to induce blood clotting.
It is also binding for collagen and fibronectin in blood vessels and skin cells.
It is present exclusively in cartilage tissues, where it binds to choanocytes, collagen, and proteoglycans to impart structural strength.
It is the most abundant protein in the body, and it is present in the extracellular matrix as a fibrillar protein to provide structural support to cells in tissue.
Fibroblasts and endothelial cells produce it. It is found abundantly in tendons, cartilage, bones, and the skin.
The structure of collagen fibers consists of three helically wound polypeptide chains.
It is secreted by the cell in its precursor form, which is then cleaved to produce collagen depending on the cellular requirement.
Depending on the eventual structure of the fibers, the fourteen types of collagen can be classified into five main categories as follows:
- Fibrillar (Tipo I, II, III, V, XI).
- Facit (Types IX, XII, XIV).
- Short-chain (Type VIII, X).
- Membrana basal (Tipo IV).
- Other (Type VI, VII, XIII).
It imparts elasticity to tissues, allowing them to expand and contract. This quality is vital in structures such as blood vessels, lungs, skin, and nuchal ligaments.
Elastins are synthesized and secreted by fibroblasts and smooth muscle cells.
They are highly insoluble and are released as a precursor molecule on contact with a mature elastin fiber.
The precursor molecules (tropoelastins) are incorporated into the mature elastin chain.
This glycoprotein helps in the adhesion of collagen fibers to cells, which allows them to migrate through the extracellular matrix.
This occurs due to the collagen fiber binding to the transmembrane integrin, causing a cascade of processes that reorganize actin filaments in the cytoplasm.
This ultimately leads to cell migration. Fibronectins are secreted in an inactive folded form that unfolds and becomes activated by binding to integrin molecules in the event of tissue injury.
These molecules bind to platelets in the blood and cause blood clotting and wound healing.
It is found in the muscles’ basal lamina and the external lamina in a network-like structure.
This structure allows it to bind to other components of the extracellular matrix, such as collagen, heparan sulfate, and cell adhesion receptors, to achieve cell adhesion.
It also plays a role in cell migration, differentiation, and development.
Cancer cells use matrix proteolytic and metalloproteinase enzymes during cancer metastasis to alter the extracellular matrix. Cell migration from the aberrant cell is allowed and enhanced, causing cancer to spread to other tissues.
The study of the extracellular matrix components has now paved the way for the medical applications of this cellular secretion.
Studies have shown that the extracellular matrix can be used to heal and regenerate tissues.