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  • Open Access

    ARTICLE

    Force-induced Unfolding of the Focal Adhesion Targeting Domain and the Influence of Paxillin Binding

    M.R. Kaazempur Mofrad1,2, J. Golji2, N.A. Abdul Rahim2, R.D. Kamm3

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 253-266, 2004, DOI:10.3970/mcb.2004.001.253

    Abstract Membrane-bound integrin receptors are linked to intracellular signaling pathways through focal adhesion kinase (FAK). FAK tends to colocalize with integrin receptors at focal adhesions through its C-terminal focal adhesion targeting (FAT) domain. Through recruitment and binding of intracellular proteins, FAs transduce signals between the intracellular and extracellular regions that regulate a variety of cellular processes including cell migration, proliferation, apoptosis and detachment from the ECM. The mechanism of signaling through the cell is of interest, especially the transmission of mechanical forces and subsequent transduction into biological signals. One hypothesis relates mechanotransduction to conformational changes in More >

  • Open Access

    ARTICLE

    Forced Dissociation of the Strand Dimer Interface between C-Cadherin Ectodomains

    M.V. Bayas1,1, K.Schulten2,2, D. Leckb,3,3

    Molecular & Cellular Biomechanics, Vol.1, No.2, pp. 101-112, 2004, DOI:10.3970/mcb.2004.001.101

    Abstract The force-induced dissociation of the strand dimer interface in C-cadherin has been studied using steered molecular dynamics simulations. The dissociation occurred, without domain unraveling, after the extraction of the conserved trypthophans (Trp2) from their respective hydrophobic pockets. The simulations revealed two stable positions for the Trp2 side chain inside the pocket. The most internal stable position involved a hydrogen bond between the ring Ne of Trp2 and the backbone carbonyl of Glu90. In the second stable position, the aromatic ring is located at the pocket entrance. After extracting the two tryptophans from their pockets, the More >

  • Open Access

    ARTICLE

    Inhibition of focal adhesion kinase by antisense oligonucleotides enhances the sensitivity of breast cancer cells to camptothecins

    T.H. Satoh2, T.A. Surmacz3, O. Nyormoi4, C.M. Whitacre1

    BIOCELL, Vol.27, No.1, pp. 47-55, 2003, DOI:10.32604/biocell.2003.27.047

    Abstract This study shows a strong association between cell attachment to substratum and activation of β1-integrin-signaling with resistance to the camptothecin derivative topotecan (TPT) in breast cancer cells. We propose a mechanistic-driven approach to sensitize the cells to camptothecins. ZR-75-1 anchoragedependent breast cancer cell line, its derivative 9D3S suspension cells (9D3S-S), and 9D3S cells attached to fibronectin-coated plates (9D3S-A) were treated with TPT (1 µM) or CPT-11 (40 µM) for 48 h. Programmed cell death (PCD), as shown by poly(ADP-ribose) polymerase (PARP), pro-caspase-3 and pro-caspase-9 cleavage, was observed in 9D3S-S cells but not in ZR-75-1 or More >

  • Open Access

    ARTICLE

    Molecular-Dynamics Analysis of Grain-Boundary Grooving in Interconnect Films with Underlayers

    T. Iwasaki1 and H. Miura1

    CMES-Computer Modeling in Engineering & Sciences, Vol.4, No.5, pp. 551-558, 2003, DOI:10.3970/cmes.2003.004.551

    Abstract We have developed a molecular-dynamics technique for investigating migration-induced failures in interconnect films for ULSIs. This technique was used to simulate grain-boundary grooving in Al and Cu films. The simulations showed that the grain-boundary grooves are formed by atomic diffusion at the grain boundary. To clarify what kind of underlay material is effective in suppressing this diffusion, we calculated the dependence of groove depth on the kind of underlay material. The calculation showed that the groove depth of the Al film decreases in the order: Al/Ta, Al/W, and Al/TiN while that of the Cu film More >

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