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  • Open Access

    ARTICLE

    Substrate Modulation of Osteoblast Adhesion Strength, Focal Adhesion Kinase Activation, and Responsiveness to Mechanical Stimuli

    E. Takai1, R. Landesberg2, R.W. Katz2, C.T. Hung3, X.E Guo1,4

    Molecular & Cellular Biomechanics, Vol.3, No.1, pp. 1-12, 2006, DOI:10.3970/mcb.2006.003.001

    Abstract Osteoblast interactions with extracellular matrix (ECM) proteins are known to influence many cell functions, which may ultimately affect osseointegration of implants with the host bone tissue. Some adhesion-mediated events include activation of focal adhesion kinase, and subsequent changes in the cytoskeleton and cell morphology, which may lead to changes in adhesion strength and cell responsiveness to mechanical stimuli. In this study we examined focal adhesion kinase activation (FAK), F-actin cytoskeleton reorganization, adhesion strength, and osteoblast responsiveness to fluid shear when adhered to type I collagen (ColI), glass, poly-L-lysine (PLL), fibronectin (FN), vitronectin (VN), and serum… More >

  • Open Access

    ARTICLE

    Shear Force at the Cell-Matrix Interface: Enhanced Analysis for Microfabricated Post Array Detectors

    Christopher A. Lemmon1,2, Nathan J. Sniadecki3, Sami Alom Ruiz1,3, John L. Tan, Lewis H. Romer2,4,5, Christopher S. Chen3,4

    Molecular & Cellular Biomechanics, Vol.2, No.1, pp. 1-16, 2005, DOI:10.3970/mcb.2005.002.001

    Abstract The interplay of mechanical forces between the extracellular environment and the cytoskeleton drives development, repair, and senescence in many tissues. Quantitative definition of these forces is a vital step in understanding cellular mechanosensing. Microfabricated post array detectors (mPADs) provide direct measurements of cell-generated forces during cell adhesion to extracellular matrix. A new approach to mPAD post labeling, volumetric imaging, and an analysis of post bending mechanics determined that cells apply shear forces and not point moments at the matrix interface. In addition, these forces could be accurately resolved from post deflections by using images of More >

  • Open Access

    ARTICLE

    Melanoma Cell Extravasation under Flow Conditions Is Modulated by Leukocytes and Endogenously Produced Interleukin 8

    Cheng Dong1,2,3, Margaret J. Slattery2,3, Shile Liang3, Hsin-Hsin Peng2

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 145-160, 2005, DOI:10.3970/mcb.2005.002.145

    Abstract Attachment of tumor cells to the endothelium (EC) under flow conditions is critical for the migration of tumor cells out of the vascular system to establish metastases. Innate immune system processes can potentially promote tumor progression through inflammation dependant mechanisms.\nobreakspace {} White blood cells, neutrophils (PMN) in particular, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration and metastasis. Melanoma cell interaction with the EC is distinct from PMN-EC adhesion in the circulation. We found PMN increased melanoma cell extravasation, which involved initial PMN tethering on… More >

  • Open Access

    REVIEW

    Biophysical approaches for studying the integrity and function of tight junctions

    S.R.K. Vedula1, T.S. Lim2, P.J. Kausalya3, W. Hunziker3, G. Rajagopal2, C.T. Lim1,4

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 105-124, 2005, DOI:10.3970/mcb.2005.002.105

    Abstract Cell-cell adhesion is an extremely important phenomenon as it influences several biologically important processes such as inflammation, cell migration, proliferation, differentiation and even cancer metastasis. Furthermore, proteins involved in cell-cell adhesion are also important from the perspective of facilitating better drug delivery across epithelia. The adhesion forces imparted by proteins involved in cell-cell adhesion have been the focus of research for sometime. However, with the advent of nanotechnological techniques such as the atomic force microscopy (AFM), we can now quantitatively probe these adhesion forces not only at the cellular but also molecular level. Here, we More >

  • Open Access

    REVIEW

    Catch Bonds: Physical Models and Biological Functions

    Cheng Zhu1, Rodger P. McEver2

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 91-104, 2005, DOI:10.3970/mcb.2005.002.091

    Abstract Force can shorten the lifetimes of receptor-ligand bonds by accelerating their dissociation. Perhaps paradoxical at first glance, bond lifetimes can also be prolonged by force. This counterintuitive behavior was named catch bonds, which is in contrast to the ordinary slip bonds that describe the intuitive behavior of lifetimes being shortened by force. Fifteen years after their theoretical proposal, catch bonds have finally been observed. In this article we review recently published data that have demonstrated catch bonds in the selectin system and suggested catch bonds in other systems, the theoretical models for their explanations, and More >

  • Open Access

    ARTICLE

    Tissue expression of platelet endothelial cell adhesion molecule-1 at pre and postnatal murine development

    GRACIELA CRISTINA CALABRESE*, ROSA WAINSTOK**

    BIOCELL, Vol.28, No.3, pp. 251-258, 2004, DOI:10.32604/biocell.2004.28.251

    Abstract Endothelial cells, at the cell-cell borders, express PECAM-1, and have been implicated in vascular functions. The monoclonal antibody MEC 13.3 recognizes PECAM-1 molecule from mouse vessels and allows to analyze the ontogeny of mouse endothelium. At the present, little is known about the molecular basis of differentiation pathways of endothelial cells, that enables its morphological heterogeneity. The purpose of this study was to analyze the pattern of PECAM-1 expression, employing monoclonal antibody MEC 13.3, in cellular suspensions obtained from different mouse organs at pre and postnatal stages.
    Fluorescence activated cell sorter analysis showed a different… More >

  • 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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