Extracellular matrix Table

A domain family that is considerably expanded in nematodes, relative to vertebrates, is the zona pellucida (ZP) domain (Bork and Sander, 1992). In database searches this domain was found in C. elegans cuticlin-1 (cut-1), a component of the nematode cuticle (Sebastiano et al., 1991), and 33 other C. elegans proteins (Table II). On the basis of disulfide-linked domains that accompany the ZP domain in these proteins, it is likely that they localize to the worm s extracellular matrix. Indeed, it is possible that most of these proteins are components of the worm cuticle. The cuticle structure is the multilayered elastic exoskeleton that determines the worm s body shape. Although vertebrates lack an equivalent... 

TABLE 2.2 Important extracellular matrix and adhesive components use as receptors by pathogens°... 

Table L Examples of specific amino acid sequences in extracellular matrix molecules, which represent ligands for cell adhesion receptors and can be used in tissue engineering...

Heparin has been found to bind a large number of proteins (Table 3). The biological activity of heparin and related polysaccharides is usually ascribed to their interaction with heparin-binding proteins. These proteins can be classified into classes including (1) enzymes, (2) protease inhibitors, (3) lipoproteins, (4) growth factors, (5) chemokines, (6) selectins, (7) extracellular matrix proteins, (8) receptor proteins, (9) viral coat proteins, (10) nuclear proteins, and (11) other proteins (1). Many heparin-binding proteins are enzymes and enzyme inhibitors. For example, proteases in the coagulation cascade, such as factors Ha, IXa, Xa, Xlla, and Villa, are heparin-... 

Tissue also contains some endogenous species that exhibit fluorescence, such as aromatic amino acids present in proteins (phenylalanine, tyrosine, and tryptophan), pyridine nucleotide enzyme cofactors (e.g., oxidized nicotinamide adenine dinucleotide, NADH pyridoxal phosphate flavin adenine dinucleotide, FAD), and cross-links between the collagen and the elastin in extracellular matrix.100 These typically possess excitation maxima in the ultraviolet, short natural lifetimes, and low quantum yields (see Table 10.1 for examples), but their characteristics strongly depend on whether they are bound to proteins. Excitation of these molecules would elicit background emission that would contaminate the emission due to implanted sensors, resulting in baseline offsets or even major spectral shifts in extreme cases therefore, it is necessary to carefully select fluorophores for implants. It is also noteworthy that the lifetimes are fairly short, such that use of longer lifetime emitters in sensors would allow lifetime-resolved measurements to extract sensor emission from overriding tissue fluorescence. 

The MMPs are a family of zinc-dependent neutral endopep-tidases that share structural domains but differ in substrate specificity, cellular sources, and inductivity (Table I). All the MMPs are important for remodeling of the extra cellular matrix and share the following functional features (/) they degrade extracellular matrix components, including fibronectin, collagen, elastin, proteoglycans, and laminin, (//) they are secreted in a latent proform and require activation for proteolytic activity, (///) they contain zinc at their active site and need calcium for stability, (/V) they function at neutral pH, and (v) they are inhibited by specific tissue inhibitors of metalloproteinases (TIMPs). 

There are several pro-angiogenic factors that promote angiogenesis (Table 2). Those include growth factors, hormone receptor agonists, pro-coagulants, extracellular matrix proteins, or glycosaminoglycans (GAGs). 

Besides the compounds already mentioned, some adherent cell lines need proteins of the extracellular matrix (ECM) for efficient adherence to the support and for cell growth. Many ECM proteins, such as fibronectin, are present in serum, as shown in Table 5.3, while others, such as collagen, are secreted by cells constitutively or after their stimulation with a growth factor. Another ECM protein, laminin, can... 

All of these structures have an epithelial lining that lies at the interface as well as extracellular matrix including basement membranes and loose connective tissue that supports the cellular layers (Table 3.2). These tissues are similar in their general structure they all have an inner cellular layer, supportive connective tissue, and an outer cellular layer. It is important to be familiar with the structure of these tissues to be able to analyze how external and internal mechanical forces are transduced at both the macroscopic and microscopic level into and out of cells. The effect of mechanical loading on these tissues is complex, but as discussed above, with increased frictional forces on the epidermis, the surface layer of skin actually increases the thickness of the epidermis. 

Collagen is the major insoluble fibrous protein in the extracellular matrix and in connective tissue 80-90% of the collagen in the body consists of types 1, It and 111 (Table 12.2). The collagen superfamily consists of at least 20 collagen types, with as many as 38 distinct polypeptide chains and more than 15 additional proteins that have collagen-like domains. 

The Pi integrins are also known as the very late antigen (VLA) subfamily because they were first identified on lymphocytes several days after activation.31 At present there are six members, all of which bind to proteins of the extracellular matrix (see Table 6.1). Unlike the other molecules, VLA-4 (CD49d) is found on the majority of unstimulated T lymphocytes, its expression being higher on memory than naive cells.32 It contributes to T-cell adhesion to inflamed endothelium by interacting with VCAM-1 and, as we shall see later, VLA-4 facilitates T-cell infiltration across the BBB in EAE. 

The selection of vehicle not only facilitates targeting to specific tissues but will also influence localization of the sensitizer within the cells (Jori, 1992, 1996). Liposome-, lipoprotein-, or emulsion-delivered sensitizers tend to be released inside tumor cells and may cause damage at the level of lysosomes and endoplasmatic reticulum. Photosensitizers dissolved in aqueous solutions tend to cause damage to cytoplasmic and mitochondrial membranes, whereas albumin-carried substances are mainly deposited in the extracellular matrix. Features of photosensitizer medication that can be affected by the vehicle are given in Table 15.2. 

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