Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia.1 In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.1,2 More than 100 years later, Staphylococcus aureus remains a versatile and dangerous pathogen in humans. The frequencies of both community-acquired and hospital-acquired staphylococcal infections have increased steadily, with little change in overall mortality. Treatment of these infections . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199808203390806?articleTools=true

Staphylococcus aureus infections.

Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.

https://science.sciencemag.org/content/sci/238/4826/491.full.pdf

New perspectives in cell adhesion : RGD and integrins

The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology of chroni...

Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation

Two complementary strategies can be used in the fabrication of molecular biomaterials. In the 'top-down' approach, biomaterials are generated by stripping down a complex entity into its component parts (for example, paring a virus particle down to its capsid to form a viral cage). This contrasts with the 'bottom-up' approach, in which materials are assembled molecule by molecule (and in some cases even atom by atom) to produce novel supramolecular architectures. The latter approach is likely to become an integral part of nanomaterials manufacture and requires a deep understanding of individual molecular building blocks and their structures, assembly properties and dynamic behaviors. Two key elements in molecular fabrication are chemical complementarity and structural compatibility, both of which confer the weak and noncovalent interactions that bind building blocks together during self-assembly. Using natural processes as a guide, substantial advances have been achieved at the interface of nanomaterials and biology, including the fabrication of nanofiber materials for three-dimensional cell culture and tissue engineering, the assembly of peptide or protein nanotubes and helical ribbons, the creation of living microlenses, the synthesis of metal nanowires on DNA templates, the fabrication of peptide, protein and lipid scaffolds, the assembly of electronic materials by bacterial phage selection, and the use of radiofrequency to regulate molecular behaviors.

http://users.isr.ist.utl.pt/~sm3/biomedica/tissue-engeneering/Tiss_eng_3.pdf

Fabrication of novel biomaterials through molecular self-assembly.

Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

Matrix Metalloproteinases: A Review

Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin.

Among the many activities of antigen-triggered lymphocytes may be the control of fibroblast function. Thymus-dependent lymphocytes challenged with the specific antigen, dinitrophenylated ovalbumin or tetanus toxoid produced a nondialyzable factor(s) capable of causing dermal fibroblasts to undergo DNA synthesis. These fibroblasts, which exhibit basal proliferative levels in the absence of serum, responded to the lymphocyte factor with maximal thymidine incorporation at 48 to 72 hr. In addition, these activated fibroblasts significantly increased their production of protein of both the collagenous and noncollagenous types. This increase in protein synthesis preceded maximal proliferation. Thus, the fibroplasia consisting of increased numbers of fibroblasts and of increased collagen deposition associated with chronic inflammatory diseases may be the direct consequence of a specific antigenic challenge.

Lymphocyte-Mediated Activation of Fibroblast Proliferation and Collagen Production

The active migration of tumor cells through extracellular matrices has been proposed to play a role in certain aspects of metastasis. Metastatic tumor cells migrate in vitro in response to substratum-bound adhesive glycoproteins such as fibronectin. The present studies use affinity-purified proteolytic fragments of fibronectin to determine the nature of adhesion- and/or motility-promoting domains within the protein. Two distinct fragments were identified with cell adhesion-promoting activities. By a number of criteria, the adhesive activity promoted by these two fragments was distinct. One fragment, a 75-kD tryptic fragment purified by monoclonal antibody chromatography, promoted the adhesion, spreading, and haptotactic motility of melanoma cells. Experiments using a synthetic cell attachment peptide in solution indicated that at least part of the attachment activity exhibited by the 75-kD fragment is mediated by the sequence arg-gly-asp-ser. It was not possible to demonstrate migration-stimulating activity using a small (11.5 kD) peptic fragment containing this sequence (Pierschbacher, M.D., E. G. Hayman, and E. Ruoslahti, 1981, Cell, 26:259-267) suggesting that another cell-binding activity within the 75 kD fragment distinct from arg-gly-asp-ser might be required for motility. The second fragment that stimulated melanoma adhesion was a 33-kD tryptic/catheptic carboxyl-terminal heparin-binding fragment, which is localized to the A chain of fibronectin. This fragment promotes adhesion and spreading but not the motility of these cells. Melanoma adhesion to this heparin-binding fragment was sensitive to the effects of cycloheximide, which contrasted adhesion to the haptotaxis-promoting fragment. Importantly, these studies illustrate that haptotaxis in response to fibronectin is not due to simple adhesion gradients of this protein. The results are discussed in light of a model for multiple distinct cell surface constituents mediating cell adhesion and motility on fibronectin.

/pdf/human-fibronectin-contains-distinct-adhesion-and-motility-448eaetgw9.pdf

Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells.

Laminin is a large (greater than 850-kdalton) glycoprotein that is localized within basement membranes. Recent work has indicated that this protein is present within the endoneurium of mouse sciatic nerve. Furthermore, it has been shown that a rat Schwannoma cell line, RN22F, produced laminin and that laminin promoted the attachment of these cells to bacterial plastic. This report presents evidence that RN22F cells migrate in vitro to laminin in a concentration-dependent fashion. Laminin was extracted from the mouse EHS tumor and purified by molecular sieve and heparin-agarose affinity chromatography. The migration of Schwannoma cells to laminin, as assessed in a microwell modified Boyden chamber, was inhibited in a dose-dependent manner by affinity-purified antilaminin antibody. Zigmond-Hirsch checkerboard analysis experiments indicated that laminin stimulated both random and directed movement of RN22F cells. Additionally, reversal of the laminin gradient in the chambers also stimulated RN22F migration in a concentration-dependent manner, suggesting that directed migration of RN22F cells was due to a substratum-bound laminin (haptotaxis) as opposed to cell movement in response to fluid-phase laminin (chemotaxis). Binding studies using [3H]laminin demonstrated that laminin bound to the filter surface under the assay conditions used, and support the contention that cells are migrating to substrate-bound material. Furthermore, RN22F cells were shown to migrate on filters coated with laminin in the absence of additional fluid-phase laminin. The magnitude of this response could be altered by changing the relative density of bound laminin. In contrast, fibronectin promoted only marginal migration of RN22F cells. Collectively, these observations indicate that haptotaxis may be a mechanism by which laminin may guide cells during development and raise the possibility that it may be involved in peripheral nervous system myelination.

/pdf/migration-by-haptotaxis-of-a-schwann-cell-tumor-line-to-the-58go5ynm1b.pdf

Migration by haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin.

Laminin and type IV collagen were compared for the ability to promote aortic endothelial cell adhesion and directed migration in vitro. Substratum-adsorbed IV promoted aortic endothelial cell adhesion in a concentration dependent fashion attaining a maximum level 141-fold greater than controls within 30 min. Aortic endothelial cell adhesion to type IV collagen was not inhibited by high levels (10(-3) M) of arginyl-glycyl-aspartyl-serine. In contrast, adhesion of aortic endothelial cells on laminin was slower, attaining only 53% of the adhesion observed on type IV collagen by 90 min. Type IV collagen when added to the lower well of a Boyden chamber stimulated the directional migration of aortic endothelial cells in a concentration dependent manner with a maximal response 6.9-fold over control levels, whereas aortic endothelial cells did not migrate in response to laminin at any concentration (.01-2.0 X 10(-7) M). Triple helix-rich fragments of type IV collagen were nearly as active as intact type IV collagen in stimulating both adhesion and migration whereas the carboxy terminal globular domain was less active at promoting adhesion (36% of the adhesion promoted by intact type IV collagen) or migration. Importantly, aortic endothelial cells also migrate to substratum adsorbed gradients of type IV collagen suggesting that the mechanism of migration is haptotactic in nature. These results demonstrate that the aortic endothelial cell adhesion and migration is preferentially promoted by type IV collagen compared with laminin, and has a complex molecular basis which may be important in angiogenesis and large vessel repair.

/pdf/differential-effects-of-laminin-intact-type-iv-collagen-and-4vc749ayb2.pdf

James B. McCarthy

Papers

Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin.

Lymphocyte-Mediated Activation of Fibroblast Proliferation and Collagen Production

Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells.

Migration by haptotaxis of a Schwann cell tumor line to the basement membrane glycoprotein laminin.

Differential effects of laminin, intact type IV collagen, and specific domains of type IV collagen on endothelial cell adhesion and migration.