Extracellular matrix
Encyclopedia
In biology
, the extracellular matrix (ECM) is the extracellular
part of animal tissue that usually provides structural support to the animal 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
. Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces). Gels of polysaccharide
s and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM. Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest.
s, and acts as a local depot for them. 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 as metastasis often involves the destruction of extracellular matrix by enzymes such as serine
and threonine protease
s and matrix metalloproteinase
s.
. Once secreted they then aggregate with the existing matrix.
The ECM is composed of an interlocking mesh of fibrous protein
s and glycosaminoglycan
s (GAGs).
s and are usually attached to extracellular matrix proteins to form proteoglycan
s (hyaluronic acid is a notable exception, see below). Proteoglycans have a net negative charge that attracts positively charged sodium ions (Na+) which attracts water molecules via osmosis, 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.
(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 surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligand
s and regulates a wide variety of biological activities, including developmental processes, angiogenesis
, blood coagulation and tumour metastasis
.
In the extracellular matrix, especially basement membrane
s, the multi-domain
proteins perlecan
, agrin
and collagen XVIII
are the main proteins to which heparan sulfate is attached.
s contribute to the tensile strength of cartilage, tendon
s, ligament
s and walls of the aorta
. They have also been known to affect neuroplasticity
.
s have a variable sulfate content and unlike many other GAGs, do not contain uronic acid
. They are present in the cornea
, cartilage, bone
s and the horns
of animal
s.
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 significant amounts 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.
Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation
and tumor
development. It interacts with a specific transmembrane receptor, CD44
.
s are, in most animals, the most abundant protein in the ECM. In fact, collagen is the most abundant protein in the human body and accounts for 90% of bone matrix protein content. 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 protease
s to allow extracellular assembly. Diseases such as osteogenesis imperfecta
and epidermolysis bullosa
are linked with genetic defects in collagen-encoding gene
s. The collagen can be divided into several families according to the types of structure they form:
s, 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, in skin
, and the ligamentum nuchae, and these tissues contain high amounts of elastins. Elastins are synthesized by fibroblast
s and smooth muscle
cells. Elastins are highly insoluble, and tropoelastin
s 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.
s are proteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Fibronectins bind collagen and cell surface integrin
s, 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 dimer
s so that they can function properly. Fibronectins also help at the site of tissue injury by binding to platelet
s during blood clotting and facilitating cell movement to the affected area during wound healing.
s are proteins found in the basal lamina
e 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 entactin
s.
filaments of the cell, and hemidesmosomes, connecting the ECM to intermediate filaments such as keratin
. 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
.
Fibroblast
s 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
. Chondrocyte
s are found in cartilage
and produce the cartilagenous matrix. Osteoblast
s are responsible for bone formation.
cells are tessellated
to form tissue
s. 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
microfibril
s 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.
In terms of injury repair and tissue engineering
, the extracellular matrix serves two main purposes. First, it prevents the immune system from triggering from the injury and responding with inflammation and scar tissue. Next, it facilitates the surrounding cells to repair the tissue instead of forming scar tissue.
For medical applications, the cells required are usually extracted from pig bladder
s, an easily accessible and relatively unused source. It is currently being used regularly to treat ulcers by closing the hole in the tissue that lines the stomach, but further research is currently being done by many universities as well as the U.S. Government for wounded soldier applications. As of early 2007, testing was being carried out on a military base in Texas. Scientists are using a powdered form on Iraq War veterans whose hands were damaged in the war.
Not all ECM devices come from the bladder. Extracellular matrix coming from pig intestine has been used to repair "atrial septal defects" (ASD) and "patent foramen ovale" (PFO). After one year 95% of the collagen ECM in these patches is replaced by the normal soft tissue of the heart.
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...
, the extracellular matrix (ECM) is the extracellular
Extracellular
In cell biology, molecular biology and related fields, the word extracellular means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid...
part of animal tissue that usually provides structural support to the animal cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
in animals.
Extracellular matrix includes the interstitial matrix and the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
. Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces). Gels of polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
s and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM. 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, 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 factorGrowth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s, and acts as a local depot for them. Changes in physiological conditions can trigger protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
activities that cause local release of such depots. This allows the rapid and local growth factor-mediated activation of cellular functions, without de novo
De novo synthesis
De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to their being recycled after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as...
synthesis.
Formation of the extracellular matrix is essential for processes like growth, wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. An understanding of ECM structure and composition also helps in comprehending the complex dynamics of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
invasion and metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
biology as metastasis often involves the destruction of extracellular matrix by enzymes such as serine
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
and threonine protease
Threonine protease
Threnonine proteases are a family of proteolytic enzymes harbouring a threonine residue within the active site.The prototype members of this class of enzymes are the catalytic subunits of the proteasome....
s and matrix metalloproteinase
Matrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
s.
Molecular components
Components of the ECM are produced intracellularly by resident cells, and secreted into the ECM via exocytosisExocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
. Once secreted they then aggregate with the existing matrix.
The ECM is composed of an interlocking mesh of fibrous protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
s (GAGs).
Proteoglycans
GAGs are carbohydrate polymerPolymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
s and are usually attached to extracellular matrix proteins to form proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
s (hyaluronic acid is a notable exception, see below). Proteoglycans have a net negative charge that attracts positively charged sodium ions (Na+) which attracts water molecules via osmosis, 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
Heparan sulfateHeparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
(HS) is a linear polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
found in all animal tissues. It occurs as a proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
(PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
s and regulates a wide variety of biological activities, including developmental processes, angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
, blood coagulation and tumour metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
.
In the extracellular matrix, especially basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
s, the multi-domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
proteins perlecan
Perlecan
Perlecan also known as basement membrane-specific heparan sulfate proteoglycan core protein or heparan sulfate proteoglycan 2 , is a protein that in humans is encoded by the HSPG2 gene....
, agrin
Agrin
Agrin is a large proteoglycan whose best characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN...
and collagen XVIII
Type XVIII collagen
Type XVIII collagen is a type of collagen which can be cleaved to form endostatin....
are the main proteins to which heparan sulfate is attached.
Chondroitin sulfate
Chondroitin sulfateChondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities...
s contribute to the tensile strength of cartilage, tendon
Tendon
A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fasciae as they are all made of collagen except that ligaments join one bone to another bone, and fasciae connect muscles to other...
s, ligament
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...
s and walls of the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
. They have also been known to affect neuroplasticity
Neuroplasticity
Neuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
.
Keratan sulfate
Keratan sulfateKeratan sulfate
Keratan sulfate , also called keratosulfate, is any of several sulfated glycosaminoglycans that have been found especially in the cornea, cartilage, and bone. It is also synthesized in the central nervous system where it participates both in development and in the glial scar formation following an...
s have a variable sulfate content and unlike many other GAGs, do not contain uronic acid
Uronic acid
thumb|300px|The [[Fischer projection]]s of [[glucose]] and [[glucuronic acid]]. Glucose's terminal carbon's hydroxyl group has been oxidized to a [[carboxylic acid]]....
. They are present in the cornea
Cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...
, cartilage, bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s and the horns
Horn (anatomy)
A horn is a pointed projection of the skin on the head of various animals, consisting of a covering of horn surrounding a core of living bone. True horns are found mainly among the ruminant artiodactyls, in the families Antilocapridae and Bovidae...
of animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s.
Hyaluronic acid
Hyaluronic acid (or "hyaluronan") is a polysaccharidePolysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
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 significant amounts 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.
Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
development. It interacts with a specific transmembrane receptor, CD44
CD44
The CD44 antigen is a cell-surface glycoprotein involved in cell–cell interactions, cell adhesion and migration. In humans, the CD44 antigen is encoded by the CD44 gene.- Tissue distribution and isoforms :...
.
Collagen
CollagenCollagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
s are, in most animals, the most abundant protein in the ECM. In fact, collagen is the most abundant protein in the human body and accounts for 90% of bone matrix protein content. Collagens are present in the ECM as fibrillar proteins and give structural support to resident cells. Collagen is exocytosed in precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....
form (procollagen), which is then cleaved by procollagen protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s to allow extracellular assembly. Diseases such as osteogenesis imperfecta
Osteogenesis imperfecta
Osteogenesis imperfecta is a genetic bone disorder. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency of Type-I collagen...
and epidermolysis bullosa
Epidermolysis bullosa
Epidermolysis bullosa is an inherited connective tissue disease causing blisters in the skin and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal. It is caused by a mutation in the keratin or collagen gene....
are linked with genetic defects in collagen-encoding gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. The collagen can be divided into several families according to the types of structure they form:
- Fibrillar (Type I,II,III,V,XI)
- Facit (Type IX,XII,XIV)
- Short chain (Type VIII,X)
- Basement membrane (Type IV)
- Other (Type VI,VII, XIII)
Elastin
ElastinElastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
s, 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, in skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, and the ligamentum nuchae, and these tissues contain high amounts of elastins. Elastins are synthesized by fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s and smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
cells. Elastins are highly insoluble, and tropoelastin
Tropoelastin
Tropoelastin is a water-soluble molecule with a molecular weight of approximately 72,000 daltons. Multiple tropoelastin molecules covalently bind together with crosslinks to form the protein elastin that is very prevalent in the body. There is only one gene for this molecule and so only one protein...
s 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
Cutis laxa
Cutis laxa is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.-Causes:In most cases, cutis laxa is inherited...
and Williams syndrome
Williams syndrome
Williams syndrome is a rare neurodevelopmental disorder characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as...
are associated with deficient or absent elastin fibers in the ECM.
Fibronectin
FibronectinFibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
s are proteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Fibronectins bind collagen and cell surface integrin
Integrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
s, causing a reorganization of the cell's cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic 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 dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
s so that they can function properly. Fibronectins also help at the site of tissue injury by binding to platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s during blood clotting and facilitating cell movement to the affected area during wound healing.
Laminin
LamininLaminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
s are proteins found in the basal lamina
Basal lamina
The basal lamina is a layer of extracellular matrix secreted by the epithelial cells, on which the epithelium sits. It is often confused with the basement membrane, and sometimes used inconsistently in the literature, see below....
e 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 entactin
Entactin
Entactin also known as nidogen-1 is a protein that in humans is encoded by the NID1 gene. Entactin is a component of the basement membrane alongside other components such as collagen type IV, proteoglycans , laminin and fibronectin.- Function :Entactin is a member of the nidogen family of basement...
s.
Cell adhesion to the ECM
Many cells bind to components of the extracellular matrix. Cell adhesion can occur in two ways; by focal adhesions, connecting the ECM to actinActin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments of the cell, and hemidesmosomes, connecting the ECM to intermediate filaments such as keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...
. 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
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
.
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.Fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
s 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
Ground substance
Ground substance is a term for the non-cellular components of extracellular matrix which contain the fibers.It is usually not visible on slides, because it is removed during the preparation process....
. Chondrocyte
Chondrocyte
Chondrocytes are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans...
s are found in cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and produce the cartilagenous matrix. Osteoblast
Osteoblast
Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...
s are responsible for bone formation.
Extracellular matrix in plants
PlantPlant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
cells are tessellated
Tessellation
A tessellation or tiling of the plane is a pattern of plane figures that fills the plane with no overlaps and no gaps. One may also speak of tessellations of parts of the plane or of other surfaces. Generalizations to higher dimensions are also possible. Tessellations frequently appeared in the art...
to form tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s. The cell wall
Cell wall
The cell wall is the tough, usually flexible but sometimes fairly rigid layer that surrounds some types of cells. It is located outside the cell membrane and provides these cells with structural support and protection, and also acts as a filtering mechanism. A major function of the cell wall is to...
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
Cellulose
Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
microfibril
Microfibril
The microfibril is a very fine fibril, or fiber-like strand, consisting of glycoproteins and cellulose. It is usually, but not always, used as a general term in describing the structure of protein fiber, examples are hair and sperm tail. Its most frequently observed structural pattern is 9+2...
s embedded in a matrix of glycoproteins such as hemicellulose
Hemicellulose
A hemicellulose is any of several heteropolymers , such as arabinoxylans, present along with cellulose in almost all plant cell walls. While cellulose is crystalline, strong, and resistant to hydrolysis, hemicellulose has a random, amorphous structure with little strength...
, pectin
Pectin
Pectin is a structural heteropolysaccharide contained in the primary cell walls of terrestrial plants. It was first isolated and described in 1825 by Henri Braconnot...
, and extensin
Extensin
Extensins are a family of flexuous, rodlike, hydroxyproline-rich glycoproteins of the plant cell wall, discovered by Derek T.A. Lamport at the University of Cambridge....
. 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
Plasmodesmata
Plasmodesmata are microscopic channels which traverse the cell walls of plant cells and some algal cells, enabling transport and communication between them. Species that have plasmodesmata include members of the Charophyceae, Charales and Coleochaetales , as well as all embryophytes, better known...
(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.
Medical Applications
Extracellular Matrix cells have been found to cause regrowth and healing of tissue. In human fetuses, for example, the extracellular matrix works with stem cells to grow and regrow all parts of the human body, and fetuses can regrow anything that gets damaged in the womb. Scientists have long believed that the matrix stops functioning after full development. It has been used in the past to help horses heal torn ligaments, but it is being researched further as a device for tissue regeneration in humans.In terms of injury repair and tissue engineering
Tissue engineering
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physio-chemical factors to improve or replace biological functions...
, the extracellular matrix serves two main purposes. First, it prevents the immune system from triggering from the injury and responding with inflammation and scar tissue. Next, it facilitates the surrounding cells to repair the tissue instead of forming scar tissue.
For medical applications, the cells required are usually extracted from pig bladder
Pig bladder
Pig bladder is the bladder of a domestic pig, similar to the human urinary bladder. Today, this hollow organ has various applications in medicine, and in traditional cuisines and customs...
s, an easily accessible and relatively unused source. It is currently being used regularly to treat ulcers by closing the hole in the tissue that lines the stomach, but further research is currently being done by many universities as well as the U.S. Government for wounded soldier applications. As of early 2007, testing was being carried out on a military base in Texas. Scientists are using a powdered form on Iraq War veterans whose hands were damaged in the war.
Not all ECM devices come from the bladder. Extracellular matrix coming from pig intestine has been used to repair "atrial septal defects" (ASD) and "patent foramen ovale" (PFO). After one year 95% of the collagen ECM in these patches is replaced by the normal soft tissue of the heart.
External links
- ANAT3231 Lecture 08 Extracellular Matrix - Lecture about extracellular matrix from UNSW Cell Biology website.
- Extracellular matrix: review of its roles in acute and chronic wounds
- Usage of Extracellular Matrix from pigs to regrow human extremities
- "The Extracellular Matrix of Animals", from Chapter 19 of The Molecular Biology of the Cell, 4th edition, Alberts et al.
- Biology, John W. Kimball. An online Biology textbook.
- http://news.bbc.co.uk/1/hi/health/7354458.stm, The man who grew a finger, By Matthew Price, BBC news
- Sound Medicine - Heart Tissue Regeneration - July 19 interview discussing ECM and its uses in cardiac tissue repair (requires MP3 playback).
- Growing Body Parts - A December 2009 report by 60 Minutes