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  • Open Access

    ARTICLE

    Effects of Biglycan Deficiency on Myocardial Infarct Structure and Mechanics

    Patrick H. Campbell∗,†, Darlene L. Hunt∗,†, Ying Jones, Fred Harwood§, David Amiel§, Jeffrey H. Omens†,¶, Andrew D. McCulloch†,||

    Molecular & Cellular Biomechanics, Vol.5, No.1, pp. 27-36, 2008, DOI:10.3970/mcb.2008.005.027

    Abstract Biglycan, a small leucine-rich proteoglycan, has been shown to interact with extracellular matrix (ECM) collagen and may influence fibrillogenesis. We hypothesized that biglycan contributes to post-myocardial infarction (MI) scar development and that the absence of biglycan would result in altered scar structure and mechanics. Anterior MI was induced in biglycan hemizygous null and wild-type mice by permanent ligation of the left coronary artery. The initial extent of ischemic injury was similar in the two groups, as was the infarct size after 30 days, although there was some tendency toward reduced expansion in the biglycan-null. Electron microscopy revealed that collagen fibrils… More >

  • Open Access

    ARTICLE

    Stability of Molecular Adhesion Mediated by Confined Polymer Repellers and Ligand-Receptor Bonds

    Jizeng Wang*, Jin Qian*, Huajian Gao∗,†

    Molecular & Cellular Biomechanics, Vol.5, No.1, pp. 19-26, 2008, DOI:10.3970/mcb.2008.005.019

    Abstract Experiments have shown that stable adhesion of a variety of animal cells on substrates prepared with precisely controlled ligand distribution can be formed only if the ligand spacing is below 58 nm. To explain this phenomenon, here we propose a confined polymer model to study the stability of molecular adhesion mediated by polymer repellers and ligand-receptor bonds. In this model, both repellers and binders are treated as wormlike chains confined in a nanoslit, and the stability of adhesion is considered as a competition between attractive interactions of ligand-receptor binding and repulsive forces due to the size mismatch between repellers and… More >

  • Open Access

    ARTICLE

    Blood Flow Patterns in the Proximal Human Coronary Arteries: Relationship to Atherosclerotic Plaque Occurrence

    Jin Suo*, John N. Oshinski∗,†, D.P. Giddens∗,‡

    Molecular & Cellular Biomechanics, Vol.5, No.1, pp. 9-18, 2008, DOI:10.3970/mcb.2008.005.009

    Abstract Atherosclerotic plaques in human coronary arteries are focal manifestations of systemic disease, and biomechanical factors have been hypothesized to contribute to plaque genesis and localization. We developed a computational fluid dynamics (CFD) model of the ascending aorta and proximal sections of the right and left coronary arteries of a normal human subject using computed tomography (CT) and magnetic resonance imaging (MRI) and determined the pulsatile flow field. Results demonstrate that flow patterns in the ascending aorta contribute to a pro-atherosclerotic flow environment, specifically through localization of low and oscillatory wall shear stress in the neighborhood of coronary orifices. Furthermore, these… More >

  • Open Access

    ARTICLE

    Role of Shear Stress Direction in Endothelial Mechanotransduction

    Shu Chien*

    Molecular & Cellular Biomechanics, Vol.5, No.1, pp. 1-8, 2008, DOI:10.3970/mcb.2008.005.001

    Abstract Fluid shear stress due to blood flow can modulate functions of endothelial cells (ECs) in blood vessels by activating mechano-sensors, signaling pathways, and gene and protein expressions. Laminar shear stress with a definite forward direction causes transient activations of many genes that are atherogenic, followed by their down-regulation; laminar shear stress also up-regulates genes that inhibit EC growth. In contrast, disturbed flow patterns with little forward direction cause sustained activations of these atherogenic genes and enhancements of EC mitosis and apoptosis. In straight parts of the arterial tree, laminar shear stress with a definite forward direction has anti-atherogenic effects. At… More >

  • Open Access

    ARTICLE

    Osmoregulatory Function of Large Vacuoles Found in Notochordal Cells of the Intervertebral Disc Running Title: An Osmoregulatory Vacuole

    Christopher J. Hunter∗,†, Sophia Bianchi*, Phil Cheng, Ken Muldrew∗,‡

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 227-238, 2007, DOI:10.3970/mcb.2007.004.227

    Abstract The nucleus pulposi of many species contain residual cells from the embryonic notochord, which exhibit a very unusual appearance (large vacuoles occupying ~80% of the cell volume, surrounded by an actin cytoskeleton). While the vacuoles have been qualitatively described, their composition and function has remained elusive. Given that these cells are believed to generate and experience significant osmotic pressures in both the notochord and intervertebral disc, we hypothesized that the vacuoles may serve as osmoregulatory organelles. Using both experimental and theoretical means, we demonstrated that the vacuoles contain a low-osmolality solution, generated via ion pumps on the vacuolar membrane. During… More >

  • Open Access

    ARTICLE

    In Vitro Measurement and Calculation of Drag Force on Iliac Limb Stentgraft in a Compliant Arterial Wall Model

    A. Sinha Roy*, K. West, R. S. Rontala1, R. K. Greenberg2, R. K. Banerje1,‡

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 211-226, 2007, DOI:10.3970/mcb.2007.004.211

    Abstract Interventional treatment of aortic aneurysms using endovascular stentgrafting is a minimally invasive technique. Following device implantation, transient drag forces act on the stentgraft. When the drag force exceeds the fixation force, complications like stentgraft migration, endoleaks and stentgraft failure occur. In such a scenario the device becomes unstable, causing concern over the long-term durability of endovascular repairs. The objective of this study is: 1) to measure the drag force on iliac limb stentgraft, having a distal diameter that is half the size of the proximal end, in an in vitro experiment; 2) to calculate the drag force using blood flow--compliant… More >

  • Open Access

    ARTICLE

    Regulation of Cyclic Longitudinal Mechanical Stretch on Proliferation of Human Bone Marrow Mesenchymal Stem Cells

    Guanbin Song∗,†,‡, Yang Ju∗,†,§, Hitoshi Soyama*, Toshiro Ohashi, Masaaki Sato

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 201-210, 2007, DOI:10.3970/mcb.2007.004.201

    Abstract Mechanical stimulation is critical to both physiological and pathological states of living cells. Although a great deal of research has been done on biological and biochemical regulation of the behavior of bone marrow mesenchymal stem cells (MSCs), the influence of biomechanical factors on their behavior is still not fully documented. In this study, we investigated the modulation of mechanical stretch magnitude, frequency, and duration on the human marrow mesenchymal stem cells (hMSCs) proliferation by an in vitro model system using a mechanical stretch loading apparatus, and optimized the stretch regime for the proliferation of hMSCs. We applied 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrasodium… More >

  • Open Access

    ARTICLE

    Topological Remodeling of Cultured Endothelial Cells by Characterized Cyclic Strains

    Nooshin Haghighipour, Mohammad Tafazzoli-Shadpour, Mohammad Ali Shokrgozar, Samira Amini, Amir Amanzadeh, Mohammad Taghi Khorasani

    Molecular & Cellular Biomechanics, Vol.4, No.4, pp. 189-200, 2007, DOI:10.3970/mcb.2007.004.189

    Abstract Evaluation of mechanical environment on cellular function is a major field of study in cellular engineering. Endothelial cells lining the entire vascular lumen are subjected to pulsatile blood pressure and flow. Mechanical stresses caused by such forces determine function of arteries and their remodeling. Critical values of mechanical stresses contribute to endothelial damage, plaque formation and atherosclerosis. A device to impose cyclic strain on cultured cells inside an incubator was designed and manufactured operating with different load amplitudes, frequencies, numbers of cycles and ratios of extension to relaxation. Endothelial cells cultured on collagen coated silicon scaffolds were subjected to cyclic… More >

  • 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

    Two-Layer Passive/Active Anisotropic FSI Models with Fiber Orientation: MRI-Based Patient-Specific Modeling of Right Ventricular Response to Pulmonary Valve Insertion Surgery

    Dalin Tang*, Chun Yang, Tal Geva‡,§, Pedro J. del Nido

    Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 159-176, 2007, DOI:10.3970/mcb.2007.004.159

    Abstract A single-layer isotropic patient-specific right/left ventricle and patch (RV/LV/Patch) combination model with fluid-structure interactions (FSI) was introduced in our previous papers to evaluate and optimize human pulmonary valve replacement/insertion (PVR) surgical procedure and patch design. In this paper, an active anisotropic model with two-layer structure for ventricle wall and tissue fiber orientation was introduced to improve previous isotropic model for more accurate assessment of RV function and potential application in PVR surgery and patch design. A material-stiffening approach was used to model active heart contraction. The computational models were used to conduct ``virtual (computational)'' surgeries and test the hypothesis that… More >

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