In biology, the extracellular matrix (ECM) is a three-dimensional network of extracellular macromolecules, such as collagen, enzymes, and glycoproteins, that provide structural and biochemical support to surrounding cells.
Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces).
Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest.
Each type of connective tissue in animals has a type of ECM: collagen fibers and bone mineral comprise the ECM of bone tissue; reticular fibers and ground substance comprise the ECM of loose connective tissue; and blood plasma is the ECM of blood.
The plant ECM includes cell wall components, like cellulose, in addition to more complex signaling molecules.
Components of the ECM are produced intracellularly by resident cells and secreted into the ECM via exocytosis.
Once secreted, they then aggregate with the existing matrix.
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.
It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or ECM proteins.
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.
They have also been known to affect neuroplasticity.
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.
It interacts with a specific transmembrane receptor, CD44.
Collagens are 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.
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)
Elastins, in contrast to collagens, give elasticity to tissues, allowing them to stretch when needed and then return to their original state.
Tropoelastins are then deaminated to become incorporated into the elastin strand.
In 2016, Huleihel et al., reported the presence of DNA, RNA, and Matrix-bound nanovesicles (MBVs) within ECM bioscaffolds.
MBVs shape and size were found to be consistent with previously described exosomes.
MBVs cargo includes different protein molecules, lipids, DNA, fragments, and miRNAs.
Similar to ECM bioscaffolds, MBVs can modify the activation state of macrophages and alter different cellular properties such as; proliferation, migration and cell cycle.
MBVs are now believed to be an integral and functional key component of ECM bioscaffolds.
Cell adhesion proteins
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.
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 and nidogens.
There are many cell types that contribute to the development of the various types of extracellular matrix found in the 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.
Osteoblasts are responsible for bone formation.
Stiffness and elasticity
The elasticity of the ECM can differ by several orders of magnitude.
Cells can sense the mechanical properties of their environment by applying forces and measuring the resulting backlash.
This plays an important role because it helps regulate many important cellular processes including cellular contraction, cell migration, cell proliferation, differentiation and cell death (apoptosis).
Inhibition of nonmuscle myosin II blocks most of these effects, indicating that they are indeed tied to sensing the mechanical properties of the ECM, which has become a new focus in research during the past decade.
Effect on gene expression
Differing mechanical properties in ECM exert effects on both cell behaviour and gene expression.
Although the mechanism by which this is done has not been thoroughly explained, adhesion complexes and the actin-myosin cytoskeleton, whose contractile forces are transmitted through transcellular structures are thought to play key roles in the yet to be discovered molecular pathways.
Effect on differentiation
ECM elasticity can direct cellular differentiation, the process by which a cell changes from one cell type to another.
In particular, naive mesenchymal stem cells (MSCs) have been shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity.
Similarly stiffer matrices that mimic muscle are myogenic, and matrices with stiffnesses that mimic collagenous bone are osteogenic.
Main article: Durotaxis
The term was coined by Lo CM and colleagues when they discovered the tendency of single cells to migrate up rigidity gradients (towards more stiff substrates) and has been extensively studied since.
This complex contains many proteins that are essential to durotaxis including structural anchoring proteins (integrins) and signaling proteins (adhesion kinase (FAK), talin, vinculin, paxillin, α-actinin, GTPases etc.) which cause changes in cell shape and actomyosin contractility.
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 extracellular matrix regulates a cell's dynamic behavior.
In addition, it sequesters a wide range of cellular growth factors and acts as a local store for them.
Changes in physiological conditions can trigger protease activities that cause local release of such stores.
This allows the rapid and local growth factor-mediated activation of cellular functions without de novo synthesis.
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 proteases, threonine proteases, and matrix metalloproteinases.
Cells actively sense ECM rigidity and migrate preferentially towards stiffer surfaces in a phenomenon called durotaxis.
They also detect elasticity and adjust their gene expression accordingly which has increasingly become a subject of research because of its impact on differentiation and cancer progression.
In the brain, where hyaluronan is the main ECM component, the matrix display both structural and signaling properties.
High-molecular weight hyaluronan acts as a diffusional barrier that can modulate diffusion in the extracellular space locally.
Upon matrix degradation, hyaluronan fragments are released to the extracellular space, where they function as pro-inflammatory molecules, orchestrating the response of immune cells such as microglia.
Many cells bind to components of the extracellular matrix.
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 signalling pathways as well as association with the cellular cytoskeleton via a set of adaptor molecules such as actin.
See also: Regenerative medicine
Extracellular matrix has been found to cause regrowth and healing of tissue.
Although the mechanism of action by which extracellular matrix promotes constructive remodeling of tissue is still unknown, researchers now believe that Matrix-bound nanovesicles (MBVs) are a key player in the healing process.
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, 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 required ECM is usually extracted from pig bladders, 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 small intestine submucosa are being used to repair "atrial septal defects" (ASD), "patent foramen ovale" (PFO) and inguinal hernia.
After one year, 95% of the collagen ECM in these patches is replaced by the normal soft tissue of the heart.
Extracellular matrix proteins are commonly used in cell culture systems to maintain stem and precursor cells in an undifferentiated state during cell culture and function to induce differentiation of epithelial, endothelial and smooth muscle cells in vitro.
Extracellular matrix proteins can also be used to support 3D cell culture in vitro for modelling tumor development.
A class of biomaterials derived from processing human or animal tissues to retain portions of the extracellular matrix are called ECM Biomaterial.
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 Pluriformea and Filozoa
The importance of the extracellular matrix has long been recognized (Lewis, 1922), but the usage of the term is more recent (Gospodarowicz et al., 1979).
Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Extracellular matrix.