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Summary: Fibrinogen (Fbg) mediates platelet aggregation by binding the αIIbβ3 integrin receptor, but the interaction of the receptor with peptide motifs of Fbg remains unresolved. This paper describes the use of self-assembled monolayers (SAMs) to study the adhesion of αIIbβ3-transfected CHO cells to the GRGDS and HHLGGAKQAGDV motifs within Fbg. Cells adhered to and spread on monolayers presenting either peptide. Cell adhesion could be inhibited by either soluble peptide, demonstrating that the peptides bind competitively to the integrin. A peptide array was used to show that AGD was the minimal binding sequence in HHLGGAKQAGDV and that the receptor recognizes ligands of the form GXGDSC, where X is a hydrophobic or basic residue. This work revises our understanding of the αIIbβ3 specificity and also suggests a new class of antithrombotic agents. [Copyright &y& Elsevier]

This work reports on the role of the synergy peptide PHSRN in mediating the adhesion of cells. The attachment of baby hamster kidney cells and 3T3 Swiss fibroblasts to model substrates presenting either GRGDS or PHSRN was evaluated using self-assembled monolayers of alkanethiolates on gold presenting the peptide ligands mixed with tri(ethylene glycol) groups. These substrates permit rigorous control over the structures and densities of peptide ligands and at the same time prevent nonspecific interactions with adherent cells. Both cell types attached efficiently to monolayers presenting either the RGD or the PHSRN peptide but not to monolayers presenting scrambled peptide GRDOS or HRPSN. Cell attachment was comparable on substrates presenting either peptide ligand but less efficient than on substrates presenting the protein fibronectin. The degree of cell spreading, however, was substantially higher on substrates presenting RGD relative to PHSRN. Staining of 3T3 fibroblasts with anti-vinculin and phalloidin revealed clear cytoskeletal filaments and focal adhesions for cells attached by way of either RGD or PHSRN. Inhibition experiments showed that the attachment of 3T3 fibroblasts to monolayers presenting RGD could be inhibited completely by a soluble RGD peptide and partially by a soluble PHSRN peptide. IMR 90 fibroblast attachment to monolayers presenting PHSRN could be inhibited with anti-integrin α5 or anti-integrin β antibody. This work demonstrates unambiguously that PHSRN alone can support the attachment of cells and that the ROD and PHSRN bind competitively to the integrin receptors. [ABSTRACT FROM AUTHOR]

Looks at factors which influence the efficiency of the solid-phase synthesis of peptide-substituted alkanethiols in the preparation of substrates which support cell adhesion. Role of ligands in the interactions of mammalian cells; Strategies required to protect alkanethiol; Details on the preparation of peptides.

Cell adhesion to the extracellular matrix (ECM) is integral to the survival and function of most cells. Cells use a wide range of receptors, which function by binding ligands in the substratum and transducing signals through the intracellular domain, to regulate functions as diverse as tissue maintenance, immune response, and development. Studies that address the roles for individual receptors are important for understanding these physiological processes but are often complicated by overlapping ligand specificities between receptors. The authors says that a strategy for "rewiring" the interactions between a cell and surface to create unique ligand-receptor bonds between a cell and ECM, but at the same time preserving the biological role of the receptor. This strategy is demonstrated by rewiring a cell-surface integrin receptor for adhesion to a synthetic ligand.

Focuses on the impact of spatial display of cellular ligands and receptors on cell adhesion and communication. Determination of the cell membrane receptors; Localization of mammalian cells; Impact of electrical potential on ligand.

This paper describes a molecular strategy to restore adhesion of cells to surfaces that otherwise do not present ligands that can mediate adhesion. The approach is based on a carbonic anhydrase fusion protein that binds benzenesulfonamides and that also includes the RGD peptide motif that can bind to cell-surface integrin adhesion receptors. In this way, the fusion protein can bind to a monolayer that presents the benzenesulfonamide ligand, thereby positioning the RGD peptide at the surface, where it can mediate the adhesion and spreading of cells. This strategy may provide a general method for promoting the adhesion of cells to non-natural surfaces or to defective biological matrices. [ABSTRACT FROM AUTHOR]

Abstract: Significant efforts have addressed the role of vimentin intermediate filaments (VIF) in cell motility, shape, adhesion and their connections to microfilaments (MF) and microtubules (MT). The present work uses micropatterned substrates to control the shapes of mouse fibroblasts and demonstrates that the cytoskeletal elements are dependent on each other and that unlike MF, VIF are globally controlled. For example, both square and circle shaped cells have a similar VIF distribution while MF distributions in these two shapes are quite different and depend on the curvature of the shape. Furthermore, in asymmetric and polarized shaped cells VIF avoid the sharp edges where MF are highly localized. Experiments with vimentin null mouse embryonic fibroblasts (MEFs) adherent to polarized (teardrop) and un-polarized (dumbbell) patterns show that the absence of VIF alters microtubule organization and perturbs cell polarity. The results of this study also demonstrate the utility of patterned substrates for quantitative studies of cytoskeleton organization in adherent cells. [Copyright &y& Elsevier]

The article shows a method for generating nonuniform patterns of substrate bound ligands on the length scale of single cells. According to the authors, the resulting monolayers are compatible with studies of adherent cell culture and that cells exhibit a nonuniform distribution of FAs in response to a gradient or peptide adhesion ligand. They add the technique offers significant benefits in preparing substrates having well-defined gradients and patterns of immobilized ligands.