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  • Open Access

    ARTICLE

    Focal Adhesion Kinase Signaling Controls Cyclic Tensile Strain Enhanced Collagen I-Induced Osteogenic Differentiation of Human Mesenchymal Stem Cells

    Donald F. Ward Jr.*, William A. Williams*, Nicole E. Schapiro*, Samuel R. Christy*, Genevieve L. Weber*, Megan Salt, Robert F. Klees*, Adele Boskey, George E. Plopper ∗,‡

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 177-188, 2007, DOI:10.3970/mcb.2007.004.177

    Abstract Focal adhesion kinase (FAK) is a key integrator of integrin-mediated signals from the extracellular matrix to the cytoskeleton and downstream signaling molecules. FAK is activated by phosphorylation at specific tyrosine residues, which then stimulate downstream signaling including the ERK1/2 pathway, leading to a variety of cellular responses. In this study, we examined the effects of FAK point mutations at tyrosine residues (Y397, Y925, Y861, and Y576/7) on osteogenic differentiation of human mesenchymal stem cells exposed to collagen I and cyclic tensile strain. Our results demonstrate that FAK signaling emanating from Y397, Y925, and to a lesser extent Y576/7, but not… More >

  • Open Access

    ARTICLE

    Geometric Confinement Influences Cellular Mechanical Properties I -- Adhesion Area Dependence

    Judith Su, Xingyu Jiang, Roy Welsch, George M. Whitesides§, Peter T. C. So

    Molecular & Cellular Biomechanics, Vol.4, No.2, pp. 87-104, 2007, DOI:10.3970/mcb.2007.004.087

    Abstract Interactions between the cell and the extracellular matrix regulate a variety of cellular properties and functions, including cellular rheology. In the present study of cellular adhesion, area was controlled by confining NIH 3T3 fibroblast cells to circular micropatterned islands of defined size. The shear moduli of cells adhering to islands of well defined geometry, as measured by magnetic microrheometry, was found to have a significantly lower variance than those of cells allowed to spread on unpatterned surfaces. We observe that the area of cellular adhesion influences shear modulus. Rheological measurements further indicate that cellular shear modulus is a biphasic function… More >

  • Open Access

    ARTICLE

    Optimal Substrate Shape for Vesicle Adhesion on a Curved Substrate

    Wendong Shi∗,†, Xi-Qiao Feng*, Huajian Gao

    Molecular & Cellular Biomechanics, Vol.3, No.3, pp. 121-126, 2006, DOI:10.3970/mcb.2006.003.121

    Abstract When pulling a vesicle adhered on a substrate, both the force-displacement profile and the maximum force at pull-off are sensitively dependent upon the substrate shape. Here we consider the adhesion between a two-dimensional vesicle and a rigid substrate via long-range molecular interactions. For a given contact area, the theoretical pull-off force of the vesicle is obtained by multiplying the theoretical strength of adhesion and the contact area. It is shown that one may design an optimal substrate shape to achieve the theoretical pull-off force. More >

  • Open Access

    ARTICLE

    Kinetics Analysis of Binding between Melanoma Cells and Neutrophils

    Meghan H. Hoskins*, Cheng Dong∗,†

    Molecular & Cellular Biomechanics, Vol.3, No.2, pp. 79-88, 2006, DOI:10.3970/mcb.2006.003.079

    Abstract It has been determined previously that polymorphonuclear leukocytes, or PMNs, can facilitate melanoma cell extravasation through the endothelium under shear conditions [1,2]. The interactions between melanoma cells and PMNs are mediated by the β2-integrins expressed by PMNs and intercellular adhesion molecules (ICAM-1) expressed on melanoma cells. In this study, the kinetics of these interactions was studied using a parallel plate flow chamber. The dissociation rates were calculated under low force conditions for ICAM-1 interactions with both β2-integrins, LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), together and separately by using functional blocking antibodies on PMNs. The kinetics of PMNs stimulated with IL-8 was… More >

  • 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 (FBS). In general, surfaces that… 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 the EC, subsequent PMN capture… 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 review the structure and function… 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 their function as a mechanism… More >

  • Open Access

    ARTICLE

    First-principles Calculation of Interfacial Adhesion Strength and Electromigration for the Micro-bump Interconnect of 3D Chip Stacking Packaging

    W.H. Chen1, H.C. Cheng2,3, C.F. Yu1,3

    CMES-Computer Modeling in Engineering & Sciences, Vol.109-110, No.1, pp. 1-13, 2015, DOI:10.3970/cmes.2015.109.001

    Abstract This study aims at exploring the interfacial adhesion strength between solder bump and four typical under bump metallurgies (UBMs), i.e., Cu/Ni, Cu/TiW, Cu/Ni/Cr and /Cu/V/Cr, at atomistic scale. The average bond length and interfacial adhesion stress of the Sn-3.5Ag/Cu/Ni, Sn-3.5Ag/Cu/TiW, Sn-3.5Ag/Cu/Ni/Cr and Sn-3.5Ag/Cu/V/Cr micro-bump interconnects are calculated through the firstprinciples density functional theory (DFT) calculation to estimate the interfacial adhesion strength between the solder bump and UBMs. In addition, by investigating the electric field effect on the average bond length and adhesive stress, the combination of solder bump and UBM with better interfacial adhesion strength and electromigration resistance ability can… 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 decreases in the order: Cu/TiN,… More >

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