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  • Open Access


    Mesoscopic Biochemical Basis of Isogenetic Inheritance and Canalization: Stochasticity, Nonlinearity, and Emergent Landscape

    Hong Qian, Hao Ge

    Molecular & Cellular Biomechanics, Vol.9, No.1, pp. 1-30, 2012, DOI:10.3970/mcb.2012.009.001

    Abstract Biochemical reaction systems in mesoscopic volume, under sustained environmental chemical gradient(s), can have multiple stochastic attractors. Two distinct mechanisms are known for their origins: (a) Stochastic single-molecule events, such as gene expression, with slow gene on-off dynamics; and (b) nonlinear networks with feedbacks. These two mechanisms yield different volume dependence for the sojourn time of an attractor. As in the classic Arrhenius theory for temperature dependent transition rates, a landscape perspective provides a natural framework for the system's behavior. However, due to the nonequilibrium nature of the open chemical systems, the landscape, and the attractors it represents, are all themselves… More >

  • Open Access


    Cardioprotective Mechanisms Activated in Response to Myocardial Ischemia

    Shu Q. Liu∗,†, Brandon J. Tefft*, Di Zhang*, Derek Roberts*, Daniel J. Schuster*, Allison Wu*

    Molecular & Cellular Biomechanics, Vol.8, No.4, pp. 319-338, 2011, DOI:10.3970/mcb.2011.008.319

    Abstract Myocardial ischemia, a disorder causing myocardial infarction and malfunction, can activate various adaptive mechanisms that protect cardiomyocytes from ischemic injury. During the early hours post myocardial ischemia, injured cardiac cells can release several molecules, including adenosine, opioids, and bradykinin, which promote myocardial survival by activating the G protein signaling pathways. During a later phase about several days, myocardial ischemia induces upregulation of growth factors and cytokines, including VEGF, ILGF, HGF, and SDF-1, in the injured myocardium, contributing to cardioprotection. In addition to the injured heart, the liver participates in cardioprotection. In response to myocardial ischemia, the liver upregulates and releases… More >

  • Open Access


    Structure - Function Relationships in the Stem Cell's Mechanical World B: Emergent Anisotropy of the Cytoskeleton Correlates to Volume and Shape Changing Stress Exposure

    Hana Chang*, Melissa L. Knothe Tate∗,†,‡

    Molecular & Cellular Biomechanics, Vol.8, No.4, pp. 297-318, 2011, DOI:10.3970/mcb.2011.008.297

    Abstract In the preceding study (Part A), we showed that prescribed seeding conditions as well as seeding density can be used to subject multipotent stem cells (MSCs) to volume changing stresses and that changes in volume of the cell are associated with changes in shape, but not volume, of the cell nucleus. In the current study, we aim to control the mechanical milieu of live cells using these prescribed seeding conditions concomitant to delivery of shape changing stresses via fluid flow, while observing adaptation of the cytoskeleton, a major cellular transducer that modulates cell shape, stiffness and remodeling. We hypothesize that… More >

  • Open Access


    Structure - Function Relationships in the Stem Cell's Mechanical World A: Seeding Protocols as a Means to Control Shape and Fate of Live Stem Cells

    Joshua A. Zimmermann*, Melissa L. Knothe Tate∗,†,‡

    Molecular & Cellular Biomechanics, Vol.8, No.4, pp. 275-296, 2011, DOI:10.3970/mcb.2011.008.275

    Abstract Shape and fate are intrinsic manifestations of form and function at the cell scale. Here we hypothesize that seeding density and protocol affect the form and function of live embryonic murine mesenchymal stem cells (MSCs) and their nuclei. First, the imperative for study of live cells was demonstrated in studies showing changes in cell nucleus shape that were attributable to fixation per se. Hence, we compared live cell and nuclear volume and shape between groups of a model MSC line (C3H10T1/2) seeded at, or proliferated from 5,000 cells/cm2 to one of three target densities to achieve targeted development contexts. Cell… More >

  • Open Access


    Alteration of Viscoelastic Properties is Associated with a Change in Cytoskeleton Components of Ageing Chondrocytes from Rabbit Knee Articular Cartilage

    Wangping Duan, Lei Wei, Juntao Zhang, Yongzhuang Hao, Chunjiang Li, Hao Li, Qi Li, Quanyou Zhang, Weiyi Chen, Xiaochun Wei∗,§

    Molecular & Cellular Biomechanics, Vol.8, No.4, pp. 253-274, 2011, DOI:10.3970/mcb.2011.008.253

    Abstract The cytoskeleton network is believed to play an important role in the biomechanical properties of the chondrocyte. Ours and other laboratories have demonstrated that chondrocytes exhibit a viscoelastic solid creep behavior in vitro and that viscoelastic properties decrease in osteoarthritic chondrocytes. In this study, we aimed to understand whether the alteration of viscoelastic properties is associated with changes in cytoskeleton components of ageing chondrocytes from rabbit knee articular cartilage. Three age groups were used for this study: young (2-months-old, N=23), adult (8-months-old, N=23), and old (31-months-old, N=23) rabbit groups. Cartilage structure and proteoglycan and type II collagen content were determined… More >

  • Open Access


    Effects of Altered Restraints in β1 Integrin on the Force-Regulated Interaction between the Glycosylated I-Like Domain of β1 Integrin and Fibronectin III9-10: A Steered Molecular Dynamic Study

    Di Pan*, Yuhua Song∗,†

    Molecular & Cellular Biomechanics, Vol.8, No.3, pp. 233-252, 2011, DOI:10.3970/mcb.2011.008.233

    Abstract Cytoskeletal restraints affect force-regulated integrin function in cell adhesion. However, the structural and molecular basis underlying the effect of cytoskeletal restraints on b1 integrin binding to fibronectin is still largely unknown. In this study, we used steered molecular dynamics simulations to investigate the changes in glycosylated b1 integrin-fibronectin binding and in conformation and structure of the glycosylated b1 I-like domain-FN-III9 - 10 complex caused by altered restraints applied to b1 I-like domain. The results revealed that imposition of the increased constraints on b1 integrin increased resistance to force-induced dissociation of the b1 I-like domain-fibronectin complex. Specifically, the increased constraints enhanced… More >

  • Open Access


    Fluctuating Elastic Filaments Under Distributed Loads

    Tianxiang Su, Prashant K. Purohit∗,†

    Molecular & Cellular Biomechanics, Vol.8, No.3, pp. 215-232, 2011, DOI:10.3970/mcb.2011.008.215

    Abstract Filaments under distributed loads are common in biological systems. In this paper, we study the thermo-mechanical properties of an extensible thermally fluctuating elastic filament under distributed forces. The ground state of the filament is solved first, followed by an investigation of the thermal fluctuations around the ground state. We first consider a special case where the tangential component of the distributed force t is uniform along the filament. For the force-extension relation in this case, we show that the filament is equivalent to one under end-to-end applied force F=tL0/2 where L0 is the length of the filament. To study the… More >

  • Open Access


    On Tensegrity in Cell Mechanics

    K. Y. Volokh*

    Molecular & Cellular Biomechanics, Vol.8, No.3, pp. 195-214, 2011, DOI:10.3970/mcb.2011.008.195

    Abstract All models are wrong, but some are useful. This famous saying mirrors the situation in cell mechanics as well. It looks like no particular model of the cell deformability can be unconditionally preferred over others and different models reveal different aspects of the mechanical behavior of living cells. The purpose of the present work is to discuss the so-called tensegrity models of the cell cytoskeleton. It seems that the role of the cytoskeleton in the overall mechanical response of the cell was not appreciated until Donald Ingber put a strong emphasis on it. It was fortunate that Ingber linked the… More >

  • Open Access


    Cytoplasmic Motion Induced by Cytoskeleton Stretching and Its Effect on Cell Mechanics

    T. Zhang*

    Molecular & Cellular Biomechanics, Vol.8, No.3, pp. 169-194, 2011, DOI:10.3970/mcb.2011.008.169

    Abstract Cytoplasmic motion assumed as a steady state laminar flow induced by cytoskeleton stretching in a cell is determined and its effect on the mechanical behavior of the cell under externally applied forces is demonstrated. Non-Newtonian fluid is assumed for the multiphase cytoplasmic fluid and the analytical velocity field around the macromolecular chain is obtained by solving the reduced nonlinear momentum equation using homotopy technique. The entropy generation by the fluid internal friction is calculated and incorporated into the entropic elasticity based 8-chain constitutive relations. Numerical examples showed strengthening behavior of cells in response to externally applied mechanical stimuli. The spatial… More >

  • Open Access


    Tissue Strains Induced in Airways due to Mechanical Ventilation

    Ramana M. Pidaparti∗,†, Kittisak Koombua∗,‡

    Molecular & Cellular Biomechanics, Vol.8, No.2, pp. 149-168, 2011, DOI:10.3970/mcb.2011.008.149

    Abstract Better understanding of the stress/strain environment in airway tissues is very important in order to avoid lung injuries for patients undergoing mechanical ventilation for treatment of respiratory problems. Airway tissue strains responsible for stressing the lung's fiber network and rupturing the lung due to compliant airways are very difficult to measure experimentally. A computational model that incorporates the heterogeneity of the airways was developed to study the effects of airway tissue material properties on strain distributions within each layer of the airway wall. The geometry and boundary conditions of the tissue strain analysis were obtained from the organ-level analysis model.… More >

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