Integrins: versatility, modulation, and signaling in cell adhesion.

The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses

Adhesion receptors of the immune system.

Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

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Tissue Cells Feel and Respond to the Stiffness of Their Substrate

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

Integrins: a family of cell surface receptors.

Compositions of cross-linked collagen and a glycosaminoglycan are provided which retain characteristics rendering them useful as tissue engineering matrices or scaffolds following terminal sterilization. Also provided are methods for producing these compositions and terminally sterilized matrices or scaffolds from these compositions as well as methods of using these matrices or scaffolds as tissue engineering devices.

Collagen/glycosaminoglycan compositions for use as terminally sterilizable matrices

Entrance of precursor T cells into the thymus and their subsequent exit into the circulation are prerequisite events for development of mature T-lymphocyte characteristics (1). Thymic epithelial cells may play an integral role in thymocyte differentiation, both through direct contact and by secretion of thymic hormones (2). Thus, positional and developmental cues for maturing thymocytes may come from neighboring cell surfaces (3) or from the extracellular matrix surrounding these cells. However, the full complement of molecules involved in this differentiation process has not been identified. The influence of cell adhesion on cell growth and differentiation is well established for many cell systems (4–10) yet the interaction of lymphocytes with adhesive extracellular matrix proteins, with a few exceptions, has been largely unexplored (11–16).

Fibronectin Receptor Expression on Thymocytes

Novel synthetic Arg-Gly-Asp containing peptides which have high affinity and specificity for their receptors by virtue of restrictions on their stereochemical conformation. Such restrictions can be provided by cyclization, by inclusion into a constraining conformational structure such as a helix, by providing an additional chemical structure such as an amide or an enantiomer of a naturally occurring amino acid, or by other methods. In particular, there are provided cyclic peptides having increased affinity and selectivity for the certain receptors over that of linear, Arg-Gly-Asp-containing synthetic peptides.

Methods for the production of conformationally stabilized cell adhesion peptides

A cell adhesion peptide that supports tissue interactions on inert materials

L'invention a pour objet des agents de contraste pour imagerie par resonance magnetique (IRM), qui sont utilises pour detecter un thrombus Les agents de contraste pour IRM comprennent un agent chelatant, qui est capable de former des complexes avec un metal paramagnetique Ledit agent chelatant est associe a un compose chimique capable de se lier a une integrine L'agent de contraste pour IRM peut contenir en outre le metal paramagnetique qui forme des complexes avec ledit agent chelatant L'invention se rapporte egalement a des compositions contenant lesdits agents de contraste pour IRM et un support physiologiquement acceptable, et a l'utilisation desdits agents pour detecter la presence d'un thrombus chez un patient

Michael D. Pierschbacher

Papers

Collagen/glycosaminoglycan compositions for use as terminally sterilizable matrices

Fibronectin Receptor Expression on Thymocytes

Methods for the production of conformationally stabilized cell adhesion peptides

A cell adhesion peptide that supports tissue interactions on inert materials

Imagerie par resonance magnetique utilisee detecter un thrombus