LA MATRIU EXTRACEL·LULAR

I també juga un paper fonamental envoltant les cèl·lules durant el desenvolupament

La matriu extracel·lular és el component no cel·lular fonamental del teixit conjuntiu

Figure 19-30. Cells surrounded by spaces filled with extracellular matrix. The particular cells shown in this low-power electron micrograph are those in an embryonic chick limb bud. The cells have not yet acquired their specialized characteristics. (Fuente: Alberts et al., 1993)

Figure 19-31. The connective tissue underlying an epithelial cell sheet. It consists largely of extracellular matrix that is secreted by the fibroblasts. (Fuente: Alberts et al., 1993)

GLUCOSAMINOGLUCANS

L’Àcid Hialurònic

Figure 22-24. Structures of various glycosaminoglycans, the polysaccharide components of proteoglycans. Each of the four classes of glycosaminoglycans is formed by polymerization of a specific disaccharide and subsequent modifications including addition of sulfate groups and inversion (epimerization) of the carboxyl group on carbon 5 of D-glucuronic acid to yield L-iduronic acid. Heparan sulfate, which is ubiquitous, and its derivative heparin, found mostly in mast cells, are actually complex mixtures resulting from the degree of sulfation. Hyaluron is unsulfated. The number (n) of disaccharides typically found in each glycosaminoglycan chain is given (Fuente: Lodish et al., 2000)

PROTEOGLUCANSUnió entre d’una cadena de GAG a

la seua proteïna central en una molècula de proteoglucan

Complex d’agrecans units de forma no covalent a una

molècula d’àcid hialurònic

Figure 19-36. The linkage between a GAG chain and its core protein in a proteoglycan molecule. A specific link tetrasaccharide is first assembled on a serine residue. In most cases it is not clear how the serine residue is selected, but it seems to be a specific local conformation of the polypeptide chain, rather than a specific linear sequence of amino acids, that is recognized. The rest of the GAG chain, consisting mainly of a repeating disaccharide unit, is then synthesized, with one sugar residue being added at a time. In chondroitin sulfate the disaccharide is composed of D-glucuronic acid and N-acetyl- D-galactosamine; in heparan sulfate it is D-glucosamine (or L-iduronic acid) and N-acetyl- D-glucosamine; in keratan sulfate it is D-galactose and N-acetyl- D-glucosamine(Fuente: Alberts et al., 1993)

Figure 19-38. An aggrecan aggregate from fetal bovine cartilage. (A) Electron micrograph of an aggrecan aggregate shadowed with platinum. Many free aggrecan molecules are also seen. (B) Schematic drawing of the giant aggrecan aggregate shown in (A). It consists of about 100 aggrecan monomers noncovalently bound to a single hyaluronan chain through two link proteins that bind to both the core protein of the proteoglycan and to the hyaluronan chain, thereby stabilizing the aggregate; the link proteins are members of the hyaladherin family of hyaluronan-binding proteins discussed previously. The molecular weight of such a complex can be 108 or more, and it occupies a volume equivalent to that of a bacterium, which is about 2 x 10-12 cm. (Fuente: Alberts et al., 1993)

COL·LAGEN

Fibrilles de col·lagen al teixit conjuntiu de pell d’un embrió d’au

Figure 19-41. Electron micrograph of fibroblasts surrounded by collagen fibrils in the connective tissue of embryonic chick skin. The fibrils, which are organized into bundles that run approximately at right angles to one another, are produced by the fibroblasts. These cells contain abundant endoplasmic reticulum, where secreted proteins such as collagen are synthesized. (From C. Ploetz, E.I. Zycband, and D.E. Birk, J. Struct. Biol. 106:73-81, 1991.) (Fuente: Alberts et al., 1993)

Fibroblast

Figure 19-40. The structure of a typical collagen molecule. (A) A model of part of a single collagen a chain in which each amino acid is represented by a sphere. The chain contains about 1000 amino acid residues and is arranged as a left-handed helix with three amino acid residues per turn and with glycine as every third residue. Therefore a chain is composed of a series of triplet Gly-X-Y sequences in which X and Y can be any amino acid (although X is commonly proline and Y is commonly hydroxyproline). (B) A model of a part of a collagen molecule in which three α chains, each shown in a different color, are wrapped around one another to form a triple-stranded helical rod. Glycine is the only amino acid small enough to occupy the crowded interior of the triple helix. Only a short length of the molecule is shown; the entire molecule is 300 nm long. (From model by B.L. Trus.) (Fuente: Alberts et al., 1993)

Cadena α

Triple hèlix

Acoblament de les cadenes α formant les fibrilles de col·lagen

Figure 19-47. The intracellular and extracellular events involved in the formation of a collagen fibril. Note that collagen fibrils are shown assembling in the extracellular space contained within a large infolding in the plasma membrane. As one example of how the collagen fibrils can form ordered arrays in the extracellular space, they are shown further assembling into large collagen fibers, which are visible in the light microscope. The covalent cross-links that stabilize the extracellular assemblies are not shown. (B) Electron micrograph of a negatively stained collagen fibril reveals its typical striated appearance. (Font: Alberts et al., 1993)

Interaccions entre fibres de col·lagen fibrós i col·lagen no

fibrós

Figure 22-16. Interactions of fibrous and nonfibrous collagens. (a) Association of types II and IX collagen in a cartilage matrix. Type II forms fibrils similar in structure to type I, with a similar 67-nm periodicity, though smaller in diameter. Type IX contains two long triple helices connected at a flexible kink. At this point a chondroitin sulfate chain is linked to the α2(IX) chain. Type IX collagens are bound at regular intervals along type II fibrils, with an N-terminal nonhelical domain of type IX projecting outward. It is thought that these domains bind the collagen fibrils to the proteoglycan-rich matrix. (b) Organization of the major fibrous components in the extracellular matrix of tendons. Type I fibrils, with their characteristic 67-nm period, are all oriented longitudinally, that is, in the direction of the stress applied to the tendon. The fibrils are coated with an array of proteoglycans, as shown in blue on the right-hand fibril. Type VI fibrils bind to and link together the type I fibrils. Type VI collagen consists of thin triple helices, about 60 nm long, with globular domains at either end. The globular domains of several type VI molecules bind together, giving a “beads-on-a-string” appearance to the type VI fibril. [Part (a) after L. M. Shaw and B. Olson, 1991, Trends Biochem. Sci. 18:191; part (b) after R. R. Bruns et al., 1986, J. Cell Biol. 103:393.] (Fuente: Lodish et al., 2000)

ELASTINA

Xarxa de fibres elàstiques a un segment d’aorta de gos

Model per mostrar com les molècules d’elastina poden expandir-se i

contraure’s adoptant una forma espiral

Figure 19-49. A network of elastic fibers. These scanning electron micrographs show a low-power view of a segment of a dog's aorta (A) and a high-power view of the dense network of longitudinally oriented elastic fibers in the outer layer of the same blood vessel (B). All of the other components have been digested away with enzymes and formic acid. (From K.S. Haas, S.J. Phillips, A.J. Comerota, and J.W. White, Anat. Rec. 230:86-96, 1991.) (Fuente: Alberts et al., 1993)

Figure 19-50. Stretching a network of elastin molecules. The molecules are joined together by covalent bonds (indicated in red) to generate a cross-linked network. In the model shown each elastin molecule in the network can expand and contract as a random coil, so that the entire assembly can stretch and recoil like a rubber band. (Fuente: Alberts et al., 1993)

FIBRONECTINA Estructura modular d’una de les dos cadenes que formen una molècula de fibronectina

Figure 22-22. Structure of fibronectin chains. Only one of the two chains present in the dimeric fibronectin molecule is shown; both chains have very similar sequences. Each chain contains about 2446 amino acids and is composed of three types of repeating amino acid sequences. Circulating fibronectin lacks one or both of the type III repeats designated EDA and EDB owing to alternative mRNA splicing. At least five different sequences may occur in the IIICS region as the result of alternative splicing. Each chain contains six domains (tan ovals) containing specific binding sites for heparan sulfate, fibrin (a major constituent of blood clots), denatured forms of collagen, and cell-surface integrins. Binding to integrins is dependent on an Arg-Gly-Asp (RGD) sequence. Heparan sulfate and fibrin have binding sites in a shared domain, and each has another binding site in its own, unshared domain; these sites differ in their affinity for the ligand. [Adapted from G. Paolella, M. Barone, and F. Baralle, 1993, in M. Zern and L. Reid, eds., Extracellular Matrix, Marcel Dekker, pp. 3 – 24.] (Fuente: Lodish et al., 2000)

LA LÀMINA BASAL

Figure 19-55. Three ways in which basal laminae are organized. (Font: Alberts et al., 2002

Col·lagen Tipus IV

Figure 19-52. How type IV collagen molecules are thought to assemble into a multilayered network. The model is based on electron micrographs of rotary-shadowed preparations of these molecules assembling in vitro. (Based on P.D. Yurchenco, E.C. Tsilibary, A.S. Charonis, and H. Furthmayr, J. Histochem. Cytochem. 34:93-102, 1986.) (Fuente: Alberts et al., 1993)

An electron micrograph of an in vitro network of collagen IV. The lacy appearance of the network results from the flexibility of the molecule, the side-to-side binding between triple-helical segments (small arrows), and the interactions between C-terminal globular domains (large arrows). [P. Yurchenco and G. C. Ruben, 1987, J. Cell Biol. 105:2559.] (Fuente: Lodish et al., 2000)

Laminina

Figure 19-55. The structure of laminin. A schematic drawing of a laminin molecule is shown in (A), and electron micrographs of laminin molecules shadowed with platinum are shown in (B). This multidomain glycoprotein is composed of three polypeptides (A, B1, and B2) that are disulfide bonded into an asymmetric crosslike structure. Each of the polypeptide chains is more than 1500 amino acid residues long. Three types of α chains, three types of B1 chains, and two types of B2 chains have been identified, which in principle can associate to form 18 different laminin isoforms. Several such isoforms have been found, each with a characteristic tissue distribution. There are also several isoforms of type IV collegen, each with a distinctive tissue distribution. Thus basal laminae are chemically diverse, which is not surprising in view of their functional diversity. (B, from J. Engel et al., J. Mol. Biol. 150:97-120, 1981. © Academic Press Inc. [London] Ltd.) (Fuente: Alberts et al., 1993)

Model Actual de l’Estructura Molecular de la Làmina Basal

Figure 19-56. A current model of the molecular structure of a basal lamina. The basal lamina (A) is formed by specific interactions between the proteins type IV collagen, laminin, and entactin plus the proteoglycan perlecan (B). Arrows in (B) connect molecules that can bind directly to each other. (Based on P.D. Yurchenco and J.C. Schittny, FASEB J. 4:1577-1590, 1990.) (Fuente: Alberts et al., 2002)

DEGRADACIÓ DELS COMPONENTS DE LA MATRIU EXTRACEL·LULAR

Figure 24-16. Steps in the process of metastasis. This example illustrates the spread of a tumor from an organ such as the lung or bladder to the liver. Tumor cells may enter the bloodstream directly by crossing the wall of a blood vessel, as diagrammed here, or, more commonly perhaps, by crossing the wall of a lymphatic vessel that ultimately discharges its contents (lymph) into the bloodstream. Tumor cells that have entered a lymphatic vessel often become trapped in lymph nodes along the way, giving rise to lymph-node metastases. Studies in animals show that typically less than one in every thousand malignant tumor cells that enter the blood-stream will survive to produce a tumor at a new site. (Fuente: Alberts et al., 1993)

ADHESIÓ DE LA CÈL·LULA A LA MATRIU EXTRACEL·LULAR: INTEGRINES

Model Actual de les Subunitats Estructurals de les Integrines

Figure 19-60. The subunit structure of an integrin cell-surface matrix receptor. Electron micrographs of isolated receptors suggest that the molecule has approximately the shape shown, with the globular head projecting more than 20 nm from the lipid bilayer. By binding to a matrix protein outside the cell and to the actin cytoskeleton (via the attachment proteins talin and α-actinin) inside the cell, the protein serves as a transmembrane linker. The α and β chains are both glycosylated (not shown) and are held together by noncovalent bonds. In the fibronectin receptor shown, the α chain is made initially as a single 140,000-dalton polypeptide chain, which is then cleaved into one small transmembrane chain and one large extracellular chain that remain held together by a disulfide bond; this extracellular chain is folded into four divalent-cation-binding domains. The extracellular part of the β chain contains a repeating cysteine-rich region, where intrachain disulfide bonding occurs; the β chain has a mass of about 100,000 daltons (Fuente: Alberts et al., 1993)g

CELL-MATRIX ADHESIONSome Family Members

Ca2+- or Mg2+ -

dependence

Homophilic or Heterophilic

Cytoskeleton Associations

Cell Junction Associations

Integrins many types

yes heterophilic actin filaments (via talin, vinculin, and other proteins)

focal contacts

a6b4 yes heterophilic intermediate filaments

Hemi-desmosomes

Transmembrane Proteoglycans

syndecans no heterophilic actin filaments

noContactes Focals i Hemidesmosomes

Figure 22-9. Adhesion molecules in junctions involved in cell-matrix adhesion. Focal adhesions and hemidesmosomes are cell-matrix junctions that consist of clustered-integrin molecules. The extracellular domain of integrin binds matrix proteins, while the cytosolic domain interacts with adapter proteins. These proteins mediate attachment to stress fibers or to bundles of keratin intermediate filaments. (Fuente: Lodish et al., 2000)