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  • Open Access

    ARTICLE

    A Stochastic Analysis of a Brownian Ratchet Model for Actin-Based Motility

    Hong Qian1

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 267-278, 2004, DOI:10.3970/mcb.2004.001.267

    Abstract In recent single-particle tracking (SPT) measurements on Listeria monocytogenes motility in cells [Kuo and McGrath (2000)], the actin-based stochastic dynamics of the bacterium movement has been analyzed statistically in terms of the mean-square displacement (MSD) of the trajectory. We present a stochastic analysis of a simplified polymerization Brownian ratchet (BR) model in which motions are limited by the bacterium movement. Analytical results are obtained and statistical data analyses are investigated. It is shown that the MSD of the stochastic bacterium movement is a monotonic quadratic function while the MSD for detrended trajectories is linear. Both the 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

    Forces Required to Initiate Membrane Tether Extrusion from Cell Surface Depend on Cell Type But Not on the Surface Molecule

    Warren D. Marcus1,2, Rodger P. McEver3, Cheng Zhu1

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 245-252, 2004, DOI:10.3970/mcb.2004.001.245

    Abstract When a cell adhered to another cell or substratum via surface proteins is forced to detach, lipid membrane tethers are often extruded from the cell surface before the protein bond dissociates. For example, during the inflammatory reaction leukocytes roll on the surface of activated endothelial cells. The rolling adhesion is mediated by interactions of selectins with their ligands, e.g., P-selectin glycoprotein ligand (PSGL)-1, which extrudes membrane tethers from the surfaces of both leukocytes and endothelial cells. Membrane tether extrusion has been suggested to regulate leukocyte rolling. Here we examine several factors that may affect forces… More >

  • Open Access

    ARTICLE

    The Effects of BclXL and Bax Over-expression on Stretch-injury Induced Neural Cell Death

    Bryan Pfister1, George Oyler2, Michael Betenbaugh3, Gang Bao4

    Molecular & Cellular Biomechanics, Vol.1, No.4, pp. 233-244, 2004, DOI:10.3970/mcb.2004.001.233

    Abstract The Bcl-2 family of proteins has recently been implicated as a possible player in the complex cascade of neural cell death due to traumatic brain injuries. However, it is unclear if the Bcl-2 pathways are activated in mechanically injured neurons. Here we report the effects of BclXL and Bax over-expression on stretch-induced neural cell death using an in vitro uniaxial stretch model of traumatic axonal injury. Specifically, YFP, YFP-tagged Bax and YFP-tagged BclXL proteins were expressed in differentiated NG108-15 cells and stretch-injury assays were carried out at different strain and strain rate combinations. As a control, insults More >

  • Open Access

    ARTICLE

    Flow dynamics in Models of Intracranial Terminal Aneurysms

    Alvaro Valencia1

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 221-232, 2004, DOI:10.3970/mcb.2004.001.221

    Abstract Flow dynamics play an important role in the pathogenesis and treatment of intracranial aneurysms. The evaluation of the velocity field in the aneurysm dome and neck is important for the correct placement of endovascular coils, and the temporal and spatial variations of wall shear stress in the aneurysm are correlated with its growth and rupture. This numerical investigation describes the hemodynamic in two models of terminal aneurysm of the basilar artery. Aneurysm models with a aspect ratio of 1.0 and 1.67 were studied. Each model was subject to physiological representative waveform of inflow for a More >

  • Open Access

    ARTICLE

    Cantilever Arrays for Multiplexed Mechanical Analysis of Biomolecular Reactions

    Min Yue1,1, Jeanne C. Stachowiak1,1,2,2, Arunava Majumdar1,1,3,3

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 211-220, 2004, DOI:10.3970/mcb.2004.001.211

    Abstract Microchips;ontaining arrays of cantilever beams have been used to mechanically detect and quantitatively analyze multiple reactions of DNA hybridization and antigen-antibody binding simultaneously. The reaction-induced deflection of a cantilever beam reflects the interplay between strain energy increase of the beam and the free energy reduction of a reaction, providing an ideal tool for investigating the connection between mechanics and chemistry of biomolecular reactions. Since free energy reduction is common for all reactions, the cantilever array forms a universal platform for label-free detection of various specific biomolecular reactions. A few such reactions and their implications in More >

  • Open Access

    ARTICLE

    On the Molecular Basis for Mechanotransduction

    Roger D. Kamm1,1,2,2, Mohammad R. Kaazempur-Mofrad1,1

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 201-210, 2004, DOI:10.3970/mcb.2004.001.201

    Abstract Much is currently known about the signaling pathways that are excited when cells are subjected to a mechanical stimulus, yet we understand little of the process by which the mechanical perturbation is transformed into a biochemical signal. Numerous theories have been proposed, and each has merit. While cells may possess many different ways of responding to stress, the existence of a single unifying principle has much appeal. Here we propose the hypothesis that cells sense mechanical force through changes in protein conformation, leading to altered binding affinities of proteins, ultimately initiating an intracellular signaling cascade More >

  • Open Access

    ARTICLE

    Determination of membrane tension during balloon distension of intestine

    H. Gregersen1, G.S. Kassab2, Y.C. Fung2

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 191-200, 2004, DOI:10.3970/mcb.2004.001.191

    Abstract During the last decades, it has become increasingly common to make balloons distension in visceral organs in vivo. In particular this is true for studies of gastrointestinal motor function and biomechanics. Balloon distension is often used for assessment of small intestinal compliance and tension based on Laplace's law for cylindrical pressure pipes. This commonly used law is valid only when the balloon-distended intestine is cylindrical. Experimentally, it is seen that the diameter of the balloon-distended intestine is not a constant, but variable in the axial direction. Hence, it is necessary to improve Laplace's law for intestinal… More >

  • Open Access

    ARTICLE

    An Improved Mathematical Approach for Determination of Molecular Kinetics in Living Cells with FRAP

    Tanmay Lele1,1, Philmo Oh1,1, Jeffrey A. Nickerson1,1,2,2, Donald E. Ingber1,1,3,3

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 181-190, 2004, DOI:10.3970/mcb.2004.001.181

    Abstract The estimation of binding constants and diffusion coefficients of molecules that associate with insoluble molecular scaffolds inside living cells and nuclei has been facilitated by the use of Fluorescence Recovery after Photobleaching (FRAP) in conjunction with mathematical modeling. A critical feature unique to FRAP experiments that has been overlooked by past mathematical treatments is the existence of an `equilibrium constraint': local dynamic equilibrium is not disturbed because photobleaching does not functionally destroy molecules, and hence binding-unbinding proceeds at equilibrium rates. Here we describe an improved mathematical formulation under the equilibrium constraint which provides a more… More >

  • Open Access

    ARTICLE

    Nonlinear Elastic and Viscoelastic Deformation of the Human Red Blood Cell with Optical Tweezers

    J. P. Mills1,1, L. Qie2,2, M. Dao1,1, C. T. Lim2,2, S. Suresh1,3

    Molecular & Cellular Biomechanics, Vol.1, No.3, pp. 169-180, 2004, DOI:10.3970/mcb.2004.001.169

    Abstract Studies of the deformation characteristics of single biological cells can offer insights into the connections among mechanical state, biochemical response and the onset and progression of diseases. Deformation imposed by optical tweezers provides a useful means for the study of single cell mechanics under a variety of well-controlled stress-states. In this paper, we first critically review recent advances in the study of single cell mechanics employing the optical tweezers method, and assess its significance and limitations in comparison to other experimental tools. We then present new experimental and computational results on shape evolution, force--extension curves, More >

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