Extracellular matrix

The extracellular matrix ( extracellular matrix, intercellular, extracellular matrix, ECM) is the proportion of animal tissue (mainly in connective tissue), which lies between the cells in the so-called intercellular space. The extracellular matrix is composed of several components, which are divided into two major groups: ground substance and fibers. The ratio of the matrix to the fiber content varies depending on the location as well as the proportion of the extracellular matrix on total tissues, due to its particular function.

In plants, one does not speak of an extracellular matrix, although these also present a substance -filled intercellular space.

  • 4.2.1 glycosaminoglycans and proteoglycans
  • 4.2.2 adhesion proteins

Basics

First you wrote - simplified seen - the main components of the extracellular matrix merely a function as " glue " ( from collagen) or as tissue internal water storage ( mucopolysaccharides, proteoglycans ) to. The ECM includes after today's perspective the whole of the macromolecules which are located outside the plasma membrane of cells in tissues and organs. So is the EZM - superficially - primarily as an attachment options for the embedded cells of all tissues in their animals. Between cells and ECM but there is always a two-way interaction. The ECM is not static, but must be understood at the molecular level than at steady state. The components of the ECM are synthesized by cells and secreted extracellularly only partially fixed on other bonds and eventually degraded intracellularly or extracellularly endocytosis. In addition, is regulated by the binding to specific components of the ECM by cell receptors, the expression of genes in the cells. Cell adhesion, cell migration, cell proliferation and the construction, alteration and removal of tissue resulting thus also from the mutual influence, the ECM and cells befalls. Thus, for example, molecules which are present as structuring proteins represent messengers among other conditions. As part of the Gordon Conference on Proteoglycans from 1998 an apt characterization of the properties of ECM components was coined. They were as demiurg: means ( according to Plato, the architect of the world is itself in and through the logos).

Functions

Macroscopic examples of the mineralized matrix of the bone, the pressure- elastic substance of the cartilage or the taut fibers of the tendon; For example, microscopically, the extracellular matrix is ​​essential throughout the body everywhere, almost every tissue is held together by the ECM, then wound each muscle fiber or any fat cell of reticular fibers, the epithelium on each body surface sits on a basal lamina, which is also part of the ECM.

From the properties of the ECM, among others, the following functions or interactions result in different tissues and organs:

  • Shaping of tissues and organs
  • Water content of the tissue
  • Elasticity of the tissue
  • Tensile strength and stability of the bones, tendons and ligaments
  • Zytokinreservoir
  • Signal transduction in tissues
  • Anchoring and correct polarity for cells
  • Influencing wound-healing processes,
  • Filtering capacity of the kidney due to their specific basement membranes

Rebuilding

The degradation and remodeling of the ECM is done primarily by matrix metalloproteinases (MMPs ), of which over 20 have been identified so far. These zinc-containing enzymes are either secreted into the extracellular matrix by appropriate cells or are located at the cell membrane (MT -MMP, membrane type MMP ), the catalytic site of the enzyme protrudes into the extracellular space. These enzymes may be present in as initially inactive precursor, which is converted to the active enzyme by cleavage of a peptide ( zymogen activation ). Various MMPs here also have a different substrate specificity. MMPs have a variety of biological meanings, as is for example known that the tumor tissue, the MMP- 2, MMP -9 and MMP -14 secrete, are particularly prone to metastasize, as expressed MMPs support the degradation of basement membranes and the establishment of the tumor 's own blood vessels.

Corresponding to the MMPs exist tissue inhibitors of metalloproteinases (English " tissue inhibitors of metalloproteinases ," TIMP ). These proteins inhibit the activity of MMPs sterically by specific binding to the catalytic sites. This allows the decomposition and conversion of the tissue are modulated by MMPs. So far, four different TIMPs are known. They are secreted as soluble proteins in the extracellular matrix by appropriate cells. TIMP -3 is an exception. This protein is mainly bound in the extracellular matrix heparan sulfate proteoglycans and permanently sequestered in the ECM (such as in the Bruch's membrane of the eye).

Components

The ECM consists of a fibrous component and liquid with the substances dissolved in it. The greatest percentage of questions here, besides water, various glycoproteins and polysaccharides. In addition, nutrients are present (such as amino acids, glucose), growth hormones, and electrolytes.

The predominant protein is the family of collagens which constitute different types of fibers and are present in almost every tissue. Elastic fibers are formed from the proteins fibrillin and elastin. There is a wide variety of Adhäsionsmatrixproteinen connecting the cells with the ECM.

The second largest group are the carbohydrates, and indeed especially glycosaminoglycans, long-chain polysaccharides of very specific building blocks. The GAGs associate with proteins and form still larger macromolecules, the proteoglycans. From the diversity and interactions of proteins, glycosaminoglycans and proteoglycans, the properties of the ECM result.

Especially in the bone contains the ECM inorganic constituents, the hydroxyapatite crystals that give bone its compressive strength.

Fibers

Family of collagens

27 different proteins from the protein family of collagens are known ( collagen I to collagen XXVII). They can be distinguished by the way they associate with each other or with other components. The following compilation of some members of the collagen family are listed. The collagens I to IV are widely used, the structures formed from them are discussed below.

Fibrillar collagens: collagens type I, II, III, V and XI

Network -forming collagens: collagen type IV ( Basalmembran! ), VIII and X

Fibrillenassoziierte collagens ( FACIT ) collagens type IX, XII and XIV

Bead -like collagens: Type VI collagen

Anchoring fibrils: collagen type VII

Collagens with transmembrane domains: collagens of type XIII and XVII

The nomenclature is misleading in one respect: only the fibers of collagen I is called collagen fibers; Other structures, such as reticular fibers are indeed constructed of a protein from the family of collagens ( in this example, collagen III ) are not referred to as collagen fibrils. Collagen IV, together with laminins, entactin and the proteoglycan perlecan basement membranes.

Collagen fibers

Collagen fibers give the fabric tensile strength. 2-20 micron thick fibers consist of collagen fibrils ( diameters up to 130 nm), which in turn are made ​​up of molecules of type I collagen.

The collagen fibers are tensile strength in the longitudinal direction, they can be as good as not stretch. Each claimed according to train connective tissue contains collagen fibers that are oriented in the direction of the load. Is a fabric as claimed in any direction, the fibers (stratum dermis, sclera, cornea, muscle fascia, dura mater, the fibrous joint capsule ) are mesh -like manner before, during stress in only one direction, the fibers are aligned in parallel (especially ligaments, tendons ), and also in bone and dentin ( dentin ) provide collagen fibers for tensile strength ( Glasknochenkrankheit! ).

Reticular fibers

Reticular fibers are made of thin bundles ( 1 micron ) of fibrils of collagen, which forms fibrils thinner than collagen I, namely the collagen III. These bundles form microscopic networks or grids. Reticular fibers are widely used, they form networks among many basal laminae, as to all capillaries, muscle, peripheral nerve fibers, fat cells, and each cell of the smooth muscle. Determining component of the ECM they are in reticular connective tissue.

Elastic fibers

Elastic fibers have an extraordinary property, namely reversible extensibility. They are made of thin fibrils of the protein fibrillin and - built an amorphous substance of the protein elastin - aligned to it. A fiber has a diameter of about 2 microns. Elastic fibers are always associated with collagen fibers to be not overstretched itself and return reversed the collagen fibers back into the original position. Are especially elastic fibers in the elastic connective tissue and cartilage from elastic, but also depending on the degree of elasticity needed in many other tissues.

Ground substance

The ground substance is the unformed part of the extracellular matrix. You fill the empty in the histological section image appearing space between the fibers. She is very heterogeneous.

Glycosaminoglycans and proteoglycans

Glycosaminoglycans ( GAGs ), long-chain polysaccharides from certain disaccharide sugars, are present in the extracellular matrix in large quantities. Here are: hyaluronic acid, heparan sulfate, dermatan sulfate, chondroitin sulfate and keratan sulfate. With the exception of hyaluronic acid, all GAGs are bound to proteins to form proteoglycans. Especially in the cartilage, the role of proteoglycans and GAGs of the capabilities of the ECM is clear. You can bind a lot of water and are so important to the properties of the ECM. Proteoglycans have a significant influence on the self-assembly of collagens ( fibrillogenesis ). In addition, proteoglycans often mediate the interactions between other matrix proteins. Finally it should be mentioned that the proteoglycans also messengers and other proteins of different functionality (eg, TGF- beta, TIMP -3, etc. ) can bind to the ECM and the pericellular matrix. Thus, they exert a great influence on the behavior of cells and are involved in assembly, dismantling and reconstruction of tissues (eg, wound healing, angiogenesis, atherosclerosis, fibrosis, dissemination of tumor cells in the metastatic setting, etc.).

Adhesion proteins

Virtually all cells have receptors with which they come into contact with the ECM. Often doing various adhesion proteins, adapter proteins or other adhesive proteins are used, which are themselves part of the ECM and the one with the other components of the matrix to interact with other cellular receptors. It is a wide variety of glycoproteins, as an example, the protein family of the laminins mentioned as further examples of the known glycoproteins vitronectin and fibronectin.

Commonly used receptors for cell adhesion is of great importance, are the integrins dar. this always recognize alpha-and beta - subunits of the integrin bound by calcium ions extracellularly together to jointly develop a corresponding amino acid binding sequence in the protein content of the ECM components. Arguably the most well-known recognition sequence which is used to matrix proteins by the integrins to cell binding, the RGD sequence (arginine -glycine -aspartate ). In addition, a plurality of cell-binding sequences in the extracellular matrix has been identified. Also could also various alpha and beta Integrins mediate the more specific cell binding to extracellular matrix components, will be described.

Swell

  • S. Ayad, R. P. Boot- Hanford, M. J. Humphries, K. E. Kadler, C. A. Shuttleworth: The Extracellular Matrix ( Facts Book ). Academic Press ( Harcourt Brace & Company, Publishers), Printed in Great Britain, pp. 3 ff ( 1998), ISBN 0-12-068911-1.
  • Cell Biology
  • Histology
Eumetazoa Demiurge Bruch's membrane
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