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  • Open Access

    ARTICLE

    Forced Dissociation of Selectin-ligand Complexes Using Steered Molecular Dynamics Simulation

    Shouqin Lü1, Mian Long1,2

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 161-178, 2005, DOI:10.3970/mcb.2005.002.161

    Abstract Selectin-ligand interactions are crucial to such biological processes as inflammatory cascade or tumor metastasis. How transient formation and dissociation of selectin-ligand bonds in blood flow are coupled to molecular conformation at atomic level, however, has not been well understood. In this study, steered molecular dynamics (SMD) simulations were used to elucidate the intramolecular and intermolecular conformational evolutions involved in forced dissociation of three selectin-ligand systems: the construct consisting of P-selectin lectin (Lec) and epidermal growth factor (EGF)-like domains (P-LE) interacting with synthesized sulfoglycopeptide or SGP-3, P-LE with sialyl Lewis X (sLeX), and E-LE with sLeX. SMD… 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

    ARTICLE

    Control of the Direction of Lamellipodia Extension through Changes in the Balance between Rac and Rho Activities

    A.L. Brock, D.E. Ingber1

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 135-144, 2005, DOI:10.3970/mcb.2005.002.135

    Abstract The direction in which cells extend new motile processes, such as lamellipodia and filopodia, can be controlled by altering the geometry of extracellular matrix adhesive islands on which individual cells are cultured, thereby altering mechanical interactions between cells and the adhesive substrate [Parker (2002)]. Here we specifically investigate the intracellular molecular signals that mediate the mechanism by which cells selectively extend these processes from the corners of polygonal-shaped adhesive islands. Constitutive activation of the small GTPase Rac within cells cultured on square-shaped islands of fibronectin resulted in the elimination of preferential extension from corners. This… More >

  • Open Access

    ARTICLE

    Evaluation of Tension in Actin Bundle of Endothelial Cells Based on Preexisting Strain and Tensile Properties Measurements

    S. Deguchi1,2, T. Ohashi2, M. Sato2

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 125-134, 2005, DOI:10.3970/mcb.2005.002.125

    Abstract Actin bundles in vascular endothelial cells (ECs) play a critical role in transmitting intracellular forces between separate focal adhesion sites. However, quantitative descriptions of tension level in single actin bundles in a physiological condition are still poorly studied. Here, we evaluated magnitude of preexisting tension in a single actin bundle of ECs on the basis of measurements of its preexisting stretching strain and tensile properties. Cultured ECs expressing fluorescently-labeled actin were treated with detergents to extract acin bundles. One end of an actin bundle was then dislodged from the substrate by using a microneedle, resulting… 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

    Collaboration between GEM4 and MCB

    X. Edward Guo1, Gang Bao1

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 89-90, 2005, DOI:10.3970/mcb.2005.002.089

    Abstract This article has no abstract. More >

  • Open Access

    ARTICLE

    On the Inaugural of MCB: Molecular & Cellular Biomechanics

    X. Edward Guo1, Gang Bao1

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 87-88, 2005, DOI:10.3970/mcb.2005.002.087

    Abstract This article has no abstract. More >

  • Open Access

    ARTICLE

    How flexible is α-actinin's rod domain?

    Muhammad H. Zaman1, Mohammad R. Kaazempur-Mofrad2

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 291-302, 2004, DOI:10.3970/mcb.2004.001.291

    Abstract α-actinin, an actin binding protein, plays a key role in cell migration, cross-links actin filaments in the Z-disk, and is a major component of contractile muscle apparatus. The flexibility of the molecule is critical to its function. The flexibility of various regions of the molecule, including the linker connecting central subunits is studied using constant force steered molecular dynamics simulations. The linker, whose structure has been a subject of debate, is predicted to be semi-flexible. The flexibility of the linker is compared to all possible segments of equal length throughout the molecule. The stretching profile More >

  • Open Access

    ARTICLE

    Endothelial cells as mechanical transducers: Enzymatic activity and network formation under cyclic strain

    A. Shukla1,1, A.R. Dunn2,2, M.A. Moses3,3, K.J. Van Vliet4,4

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 279-290, 2004, DOI:10.3970/mcb.2004.001.279

    Abstract Although it is established that endothelial cells can respond to external mechanical cues (e.g., alignment in the direction of fluid shear stress), the extent to which mechanical stress and strain applied via the endothelial cell substrate impact biomolecular and cellular processes is not well-understood. This issue is particularly important in the context of inflammation, vascular remodeling, and cancer progression, as each of these processes occurs concurrently with localized increases in strain and marked changes in molecules secreted by adjacent cells. Here, we systematically vary the level and duration of cyclic tensile strain applied to human… More >

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