Second-phase particles in A1-4.4Cu-l5Mg-0.6 Mn (2024-T3) were characterized by size and chemistry using scanning electron microscopy and associated electron-beam microanalysis methods. It was found that approximately 60% of particles greater than about 0.5 to 0.7 p.m were Al,CuMg (the S phase). This fraction corresponded to 2.7% of the total surface area. S phase particles appeared to be active with respect to the matrix phase, consistent with open-circuit potentials reported in the literature for Al,CuMg. The compound exhibited severe dealloying which resulted in the formation of Cu-rich particle remnants. Some particle remnants remained largely intact and induced pitting at their periphery once ennobled by dealloying. Other particle remnants decomposed into 10 to 100 nm Cu clusters that became detached from the alloy surface and were dispersed by mechanical action of growing corrosion product or solution movement. This observation suggests that nonfaradaic liberation of Cu from corroding 2024-T3 surfaces is possible, and provides one plausible explanation for how Cu can be redistributed across the surface by a pitting process which occurs at potentials that are hundreds of millivolts negative of the reduction potential for Cu. InfroductionHeterogeneous microstructures are intentionally developed in commercial aluminum alloys to optimize mechanical properties. Microstructural heterogeneity also arises due to impurities that are unavoidably introduced during melt processing. Unfortunately, such microstructures make Al alloys susceptible to localized corrosion during service and complicate aqueous surface finishing processes.

The ␤ subunit cytoplasmic domains of integrin adhesion receptors are necessary for the connection of these receptors to the actin cytoskeleton. The cytoplasmic protein, talin, binds to ␤ integrin cytoplasmic tails and actin filaments, hence forming an integrin-cytoskeletal linkage. We used recombinant structural mimics of ␤ 1 A, ␤ 1 D and ␤ 3 integrin cytoplasmic tails to characterize integrin-binding sites within talin. Here we report that an integrin-binding site is localized within the N-terminal talin head domain. The binding of the talin head domain to integrin ␤ tails is specific in that it is abrogated by a single point mutation that disrupts integrin localization to talin-rich focal adhesions. Integrin-cytoskeletal interactions regulate integrin affinity for ligands (activation). Overexpression of a fragment of talin containing the head domain led to activation of integrin ␣ IIb ␤ 3 ; activation was dependent on the presence of both the talin head domain and the integrin ␤ 3 cytoplasmic tail. The head domain of talin thus binds to integrins to form a link to the actin cytoskeleton and can thus regulate integrin function.

The ninth and tenth type III domains of fibronectin each contain specific cell binding sequences, RGD in FIII10 and PHSRN in FIII9, that act synergistically in mediating cell adhesion. We investigated the relationship between domain-domain orientation and synergistic adhesive activity of the FIII9 and FIII10 pair of domains. The interdomain interaction of the FIII9 -10 pair was perturbed by introduction of short flexible linkers between the FIII9 and FIII10 domains. Incremental extensions of the interdomain link between FIII9 and FIII10 reduced the initial cell attachment, but had a much more pronounced effect on the downstream cell adhesion events of spreading and phosphorylation of focal adhesion kinase. The extent of disruption of cell adhesion depended upon the length of the interdomain linker. Nuclear magnetic resonance spectroscopy of the wild type and mutant FIII9 -10 proteins demonstrated that the structure of the RGD-containing loop is unaffected by domain-domain interactions. We conclude that integrin-mediated cell adhesion to the central cell binding domain of fibronectin depends not only upon specific interaction sites, but also on the relative orientation of these sites. These data have implications for the molecular mechanisms by which integrin-ligand interactions are achieved. The regulated adhesion of cells to the extracellular matrix (ECM)1 is essential for the development and function of normal tissues, and aberrant regulation of cell adhesion is often associated with disease. Fibronectins (FNs) are adhesive proteins that are abundant in the ECM of many cell types and have a critical role in many biological processes (1). Twenty isoforms of human FN, the expression of which is developmentally regulated, can be generated as a result of alternative splicing of the primary FN transcript (2-4). The FN molecules are dimers of disulfide-linked 235-kDa monomers. Each monomer is composed of type I, type II, and type III domains (FI, FII, and FIII), identified as repeating amino acid motifs in the primary structure (5) (Fig. 1). These motifs occur in many diverse cellular and extracellular proteins (6). Separable, functional regions of the FN molecule have been identified that contain binding activities for other components of the ECM, including collagen, fibrin, and heparin (1). Cells bind to FN via the central cell binding domain (CCBD) spanning the eighth, ninth, and tenth FIII domains (FIII8 -10) (7) and via the CS1 and CS5 sites in the alternatively spliced IIICS region (8, 9) (see Fig. 1).The adhesion of cells to FN in the ECM is mediated by the integrin family of transmembrane receptors (10 -12). The minimal cell recognition sequence RGD in FIII10 has been shown previously to interact with a number of integrins including 20,21), and ␣ IIb ␤ 3 (20, 21). Integrin-mediated cell adhesion to FN results in phosphorylation of focal adhesion kinase (FAK, also known as pp125 FAK ), organization of the actin cytoskeleton, and cell spreading (22)(23)(24)(25)(26). Given the ubiquity of expression of FNs and ...

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