Extracellular matrix

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Extracellular matrix_table_infobox_0

Extracellular matrixExtracellular matrix_header_cell_0_0_0
DetailsExtracellular matrix_header_cell_0_1_0
IdentifiersExtracellular matrix_header_cell_0_2_0
LatinExtracellular matrix_header_cell_0_3_0 Matrix ExtracellularisExtracellular matrix_cell_0_3_1
Acronym(s)Extracellular matrix_header_cell_0_4_0 ECMExtracellular matrix_cell_0_4_1
MeSHExtracellular matrix_header_cell_0_5_0 Extracellular matrix_cell_0_5_1
THExtracellular matrix_header_cell_0_6_0 Extracellular matrix_cell_0_6_1

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. Extracellular matrix_sentence_0

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. Extracellular matrix_sentence_1

The animal extracellular matrix includes the interstitial matrix and the basement membrane. Extracellular matrix_sentence_2

Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces). Extracellular matrix_sentence_3

Gels of polysaccharides and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM. Extracellular matrix_sentence_4

Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest. Extracellular matrix_sentence_5

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. Extracellular matrix_sentence_6

The plant ECM includes cell wall components, like cellulose, in addition to more complex signaling molecules. Extracellular matrix_sentence_7

Some single-celled organisms adopt multicellular biofilms in which the cells are embedded in an ECM composed primarily of extracellular polymeric substances (EPS). Extracellular matrix_sentence_8

Structure Extracellular matrix_section_0

Components of the ECM are produced intracellularly by resident cells and secreted into the ECM via exocytosis. Extracellular matrix_sentence_9

Once secreted, they then aggregate with the existing matrix. Extracellular matrix_sentence_10

The ECM is composed of an interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs). Extracellular matrix_sentence_11

Proteoglycans Extracellular matrix_section_1

Glycosaminoglycans (GAGs) are carbohydrate polymers and mostly attached to extracellular matrix proteins to form proteoglycans (hyaluronic acid is a notable exception; see below). Extracellular matrix_sentence_12

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. Extracellular matrix_sentence_13

Proteoglycans may also help to trap and store growth factors within the ECM. Extracellular matrix_sentence_14

Described below are the different types of proteoglycan found within the extracellular matrix. Extracellular matrix_sentence_15

Heparan sulfate Extracellular matrix_section_2

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. Extracellular matrix_sentence_16

It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or ECM proteins. Extracellular matrix_sentence_17

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. Extracellular matrix_sentence_18

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. Extracellular matrix_sentence_19

Chondroitin sulfate Extracellular matrix_section_3

Chondroitin sulfates contribute to the tensile strength of cartilage, tendons, ligaments, and walls of the aorta. Extracellular matrix_sentence_20

They have also been known to affect neuroplasticity. Extracellular matrix_sentence_21

Keratan sulfate Extracellular matrix_section_4

Keratan sulfates have a variable sulfate content and, unlike many other GAGs, do not contain uronic acid. Extracellular matrix_sentence_22

They are present in the cornea, cartilage, bones, and the horns of animals. Extracellular matrix_sentence_23

Non-proteoglycan polysaccharide Extracellular matrix_section_5

Hyaluronic acid Extracellular matrix_section_6

Hyaluronic acid (or "hyaluronan") is a polysaccharide consisting of alternating residues of D-glucuronic acid and N-acetylglucosamine, and unlike other GAGs, is not found as a proteoglycan. Extracellular matrix_sentence_24

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. Extracellular matrix_sentence_25

Hyaluronic acid is thus found in abundance in the ECM of load-bearing joints. Extracellular matrix_sentence_26

It is also a chief component of the interstitial gel. Extracellular matrix_sentence_27

Hyaluronic acid is found on the inner surface of the cell membrane and is translocated out of the cell during biosynthesis. Extracellular matrix_sentence_28

Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation, and tumor development. Extracellular matrix_sentence_29

It interacts with a specific transmembrane receptor, CD44. Extracellular matrix_sentence_30

Proteins Extracellular matrix_section_7

Collagen Extracellular matrix_section_8

Collagens are the most abundant protein in the ECM. Extracellular matrix_sentence_31

In fact, collagen is the most abundant protein in the human body and accounts for 90% of bone matrix protein content. Extracellular matrix_sentence_32

Collagens are present in the ECM as fibrillar proteins and give structural support to resident cells. Extracellular matrix_sentence_33

Collagen is exocytosed in precursor form (procollagen), which is then cleaved by procollagen proteases to allow extracellular assembly. Extracellular matrix_sentence_34

Disorders such as Ehlers Danlos Syndrome, osteogenesis imperfecta, and epidermolysis bullosa are linked with genetic defects in collagen-encoding genes. Extracellular matrix_sentence_35

The collagen can be divided into several families according to the types of structure they form: Extracellular matrix_sentence_36

Extracellular matrix_ordered_list_0

  1. Fibrillar (Type I, II, III, V, XI)Extracellular matrix_item_0_0
  2. Facit (Type IX, XII, XIV)Extracellular matrix_item_0_1
  3. Short chain (Type VIII, X)Extracellular matrix_item_0_2
  4. Basement membrane (Type IV)Extracellular matrix_item_0_3
  5. Other (Type VI, VII, XIII)Extracellular matrix_item_0_4

Elastin Extracellular matrix_section_9

Elastins, in contrast to collagens, give elasticity to tissues, allowing them to stretch when needed and then return to their original state. Extracellular matrix_sentence_37

This is useful in blood vessels, the lungs, in skin, and the ligamentum nuchae, and these tissues contain high amounts of elastins. Extracellular matrix_sentence_38

Elastins are synthesized by fibroblasts and smooth muscle cells. Extracellular matrix_sentence_39

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. Extracellular matrix_sentence_40

Tropoelastins are then deaminated to become incorporated into the elastin strand. Extracellular matrix_sentence_41

Disorders such as cutis laxa and Williams syndrome are associated with deficient or absent elastin fibers in the ECM. Extracellular matrix_sentence_42

Extracellular vesicles Extracellular matrix_section_10

In 2016, Huleihel et al., reported the presence of DNA, RNA, and Matrix-bound nanovesicles (MBVs) within ECM bioscaffolds. Extracellular matrix_sentence_43

MBVs shape and size were found to be consistent with previously described exosomes. Extracellular matrix_sentence_44

MBVs cargo includes different protein molecules, lipids, DNA, fragments, and miRNAs. Extracellular matrix_sentence_45

Similar to ECM bioscaffolds, MBVs can modify the activation state of macrophages and alter different cellular properties such as; proliferation, migration and cell cycle. Extracellular matrix_sentence_46

MBVs are now believed to be an integral and functional key component of ECM bioscaffolds. Extracellular matrix_sentence_47

Cell adhesion proteins Extracellular matrix_section_11

Fibronectin Extracellular matrix_section_12

Fibronectins are glycoproteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Extracellular matrix_sentence_48

Fibronectins bind collagen and cell-surface integrins, causing a reorganization of the cell's cytoskeleton to facilitate cell movement. Extracellular matrix_sentence_49

Fibronectins are secreted by cells in an unfolded, inactive form. Extracellular matrix_sentence_50

Binding to integrins unfolds fibronectin molecules, allowing them to form dimers so that they can function properly. Extracellular matrix_sentence_51

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. Extracellular matrix_sentence_52

Laminin Extracellular matrix_section_13

Laminins are proteins found in the basal laminae of virtually all animals. Extracellular matrix_sentence_53

Rather than forming collagen-like fibers, laminins form networks of web-like structures that resist tensile forces in the basal lamina. Extracellular matrix_sentence_54

They also assist in cell adhesion. Extracellular matrix_sentence_55

Laminins bind other ECM components such as collagens and nidogens. Extracellular matrix_sentence_56

Development Extracellular matrix_section_14

There are many cell types that contribute to the development of the various types of extracellular matrix found in the plethora of tissue types. Extracellular matrix_sentence_57

The local components of ECM determine the properties of the connective tissue. Extracellular matrix_sentence_58

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. Extracellular matrix_sentence_59

Chondrocytes are found in cartilage and produce the cartilaginous matrix. Extracellular matrix_sentence_60

Osteoblasts are responsible for bone formation. Extracellular matrix_sentence_61

Physiology Extracellular matrix_section_15

Stiffness and elasticity Extracellular matrix_section_16

The ECM can exist in varying degrees of stiffness and elasticity, from soft brain tissues to hard bone tissues. Extracellular matrix_sentence_62

The elasticity of the ECM can differ by several orders of magnitude. Extracellular matrix_sentence_63

This property is primarily dependent on collagen and elastin concentrations, and it has recently been shown to play an influential role in regulating numerous cell functions. Extracellular matrix_sentence_64

Cells can sense the mechanical properties of their environment by applying forces and measuring the resulting backlash. Extracellular matrix_sentence_65

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). Extracellular matrix_sentence_66

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. Extracellular matrix_sentence_67

Effect on gene expression Extracellular matrix_section_17

Differing mechanical properties in ECM exert effects on both cell behaviour and gene expression. Extracellular matrix_sentence_68

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. Extracellular matrix_sentence_69

Effect on differentiation Extracellular matrix_section_18

ECM elasticity can direct cellular differentiation, the process by which a cell changes from one cell type to another. Extracellular matrix_sentence_70

In particular, naive mesenchymal stem cells (MSCs) have been shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. Extracellular matrix_sentence_71

MSCs placed on soft matrices that mimic brain differentiate into neuron-like cells, showing similar shape, RNAi profiles, cytoskeletal markers, and transcription factor levels. Extracellular matrix_sentence_72

Similarly stiffer matrices that mimic muscle are myogenic, and matrices with stiffnesses that mimic collagenous bone are osteogenic. Extracellular matrix_sentence_73

Durotaxis Extracellular matrix_section_19

Main article: Durotaxis Extracellular matrix_sentence_74

Stiffness and elasticity also guide cell migration, this process is called durotaxis. Extracellular matrix_sentence_75

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. Extracellular matrix_sentence_76

The molecular mechanisms behind durotaxis are thought to exist primarily in the focal adhesion, a large protein complex that acts as the primary site of contact between the cell and the ECM. Extracellular matrix_sentence_77

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. Extracellular matrix_sentence_78

These changes are thought to cause cytoskeletal rearrangements in order to facilitate directional migration. Extracellular matrix_sentence_79

Function Extracellular matrix_section_20

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. Extracellular matrix_sentence_80

The extracellular matrix regulates a cell's dynamic behavior. Extracellular matrix_sentence_81

In addition, it sequesters a wide range of cellular growth factors and acts as a local store for them. Extracellular matrix_sentence_82

Changes in physiological conditions can trigger protease activities that cause local release of such stores. Extracellular matrix_sentence_83

This allows the rapid and local growth factor-mediated activation of cellular functions without de novo synthesis. Extracellular matrix_sentence_84

This effect has been explored in a modelling and theoretical study wherein VEGFC, MMP2, and collagen I were used as an example. Extracellular matrix_sentence_85

Formation of the extracellular matrix is essential for processes like growth, wound healing, and fibrosis. Extracellular matrix_sentence_86

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. Extracellular matrix_sentence_87

The stiffness and elasticity of the ECM has important implications in cell migration, gene expression, and differentiation. Extracellular matrix_sentence_88

Cells actively sense ECM rigidity and migrate preferentially towards stiffer surfaces in a phenomenon called durotaxis. Extracellular matrix_sentence_89

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. Extracellular matrix_sentence_90

In the brain, where hyaluronan is the main ECM component, the matrix display both structural and signaling properties. Extracellular matrix_sentence_91

High-molecular weight hyaluronan acts as a diffusional barrier that can modulate diffusion in the extracellular space locally. Extracellular matrix_sentence_92

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. Extracellular matrix_sentence_93

Cell adhesion Extracellular matrix_section_21

Many cells bind to components of the extracellular matrix. Extracellular matrix_sentence_94

Cell adhesion can occur in two ways; by focal adhesions, connecting the ECM to actin filaments of the cell, and hemidesmosomes, connecting the ECM to intermediate filaments such as keratin. Extracellular matrix_sentence_95

This cell-to-ECM adhesion is regulated by specific cell-surface cellular adhesion molecules (CAM) known as integrins. Extracellular matrix_sentence_96

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. Extracellular matrix_sentence_97

Fibronectins bind to ECM macromolecules and facilitate their binding to transmembrane integrins. Extracellular matrix_sentence_98

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. Extracellular matrix_sentence_99

Clinical significance Extracellular matrix_section_22

See also: Regenerative medicine Extracellular matrix_sentence_100

Extracellular matrix has been found to cause regrowth and healing of tissue. Extracellular matrix_sentence_101

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. Extracellular matrix_sentence_102

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. Extracellular matrix_sentence_103

Scientists have long believed that the matrix stops functioning after full development. Extracellular matrix_sentence_104

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. Extracellular matrix_sentence_105

In terms of injury repair and tissue engineering, the extracellular matrix serves two main purposes. Extracellular matrix_sentence_106

First, it prevents the immune system from triggering from the injury and responding with inflammation and scar tissue. Extracellular matrix_sentence_107

Next, it facilitates the surrounding cells to repair the tissue instead of forming scar tissue. Extracellular matrix_sentence_108

For medical applications, the required ECM is usually extracted from pig bladders, an easily accessible and relatively unused source. Extracellular matrix_sentence_109

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. Extracellular matrix_sentence_110

As of early 2007, testing was being carried out on a military base in Texas. Extracellular matrix_sentence_111

Scientists are using a powdered form on Iraq War veterans whose hands were damaged in the war. Extracellular matrix_sentence_112

Not all ECM devices come from the bladder. Extracellular matrix_sentence_113

Extracellular matrix coming from pig small intestine submucosa are being used to repair "atrial septal defects" (ASD), "patent foramen ovale" (PFO) and inguinal hernia. Extracellular matrix_sentence_114

After one year, 95% of the collagen ECM in these patches is replaced by the normal soft tissue of the heart. Extracellular matrix_sentence_115

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_sentence_116

Extracellular matrix proteins can also be used to support 3D cell culture in vitro for modelling tumor development. Extracellular matrix_sentence_117

A class of biomaterials derived from processing human or animal tissues to retain portions of the extracellular matrix are called ECM Biomaterial. Extracellular matrix_sentence_118

In plants Extracellular matrix_section_23

Plant cells are tessellated to form tissues. Extracellular matrix_sentence_119

The cell wall is the relatively rigid structure surrounding the plant cell. Extracellular matrix_sentence_120

The cell wall provides lateral strength to resist osmotic turgor pressure, but it is flexible enough to allow cell growth when needed; it also serves as a medium for intercellular communication. Extracellular matrix_sentence_121

The cell wall comprises multiple laminate layers of cellulose microfibrils embedded in a matrix of glycoproteins, including hemicellulose, pectin, and extensin. Extracellular matrix_sentence_122

The components of the glycoprotein matrix help cell walls of adjacent plant cells to bind to each other. Extracellular matrix_sentence_123

The selective permeability of the cell wall is chiefly governed by pectins in the glycoprotein matrix. Extracellular matrix_sentence_124

Plasmodesmata (singular: plasmodesma) are pores that traverse the cell walls of adjacent plant cells. Extracellular matrix_sentence_125

These channels are tightly regulated and selectively allow molecules of specific sizes to pass between cells. Extracellular matrix_sentence_126

In Pluriformea and Filozoa Extracellular matrix_section_24

The extracellular matrix functionality of animals (Metazoa) developed in the common ancestor of the Pluriformea and Filozoa, after the Ichthyosporea diverged. Extracellular matrix_sentence_127

History Extracellular matrix_section_25

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). Extracellular matrix_sentence_128

See also Extracellular matrix_section_26

Extracellular matrix_unordered_list_1

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Extracellular matrix.