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  • 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 >

  • Open Access

    ARTICLE

    Airway Smooth Muscle Proliferation and Mechanics: Effects of AMP Kinase Agonists

    Anat Ratnovsky∗,†, Matthew Mellema*, Steven S. An∗,‡, Jeffrey J. Fredberg*, Stephanie A. Shore*

    Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 143-158, 2007, DOI:10.3970/mcb.2007.004.143

    Abstract Obesity is a risk factor for asthma. The purpose of this study was to determine whether metformin, an agent used in the treatment of an obesity-related condition (type II diabetes), might have therapeutic potential for modifying the effects of obesity on airway smooth muscle (ASM) function. Metformin acts via activation of AMP-activated protein kinase (AMPK), a cellular sensor of energy status. In cultured murine ASM cells, metformin (0.2--2 mM) caused a dose-dependent inhibition of cell proliferation induced by PDGF (10-8 M) and serotonin (10-4 M). Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-ß-D-riboruranoside (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells treated with metformin or… More >

  • Open Access

    ARTICLE

    A Multisclae Probabilisitc Framework to Model Early Steps in Tumor Metastasis

    Muhammad H. Zaman*

    Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 133-142, 2007, DOI:10.3970/mcb.2007.004.133

    Abstract Tumor metastasis is the leading cause of nearly all cancer related deaths. While several experimental and computational studies have addressed individual stages of the complex metastasis process, a comprehensive systems-biology model that links various stages of metastasis has not been put forth as of yet. In this paper we discuss the formulation and application of such a model that utilizes basic principles of cell biology, physics and mechanics to study the migratory patterns of tumor cells as they move from the parent tumor site to the connective tissue via the basement membrane. The model is first of its kind in… More >

  • Open Access

    ARTICLE

    Tensorial Description of the Geometrical Arrangement of the Fibrous Molecules in Vascular Endothelial Cells

    Wei Huang*

    Molecular & Cellular Biomechanics, Vol.4, No.3, pp. 119-132, 2007, DOI:10.3970/mcb.2007.004.119

    Abstract This work presents a tensorial description of the geometrical arrangement of the cellular molecules in the vascular endothelial cells. The geometrical arrangement of the molecules is the foundation of the mechanical properties of the molecular aggregates, which are the foundation of the physical behavior of the cells and tissues. For better studying the physical behavior of the cells and tissues, the geometrical arrangement of the cellular molecules has to be described quantitatively. In this paper, a second order molecular configuration tensor Pijg for fibrous protein in the cells is defined for quantitative measurement. Here, the subscripts i, j refer… More >

  • Open Access

    ARTICLE

    Geometric Confinement Influences Cellular Mechanical Properties II -- Intracellular Variances in Polarized Cells

    Judith Su, Ricardo R. Brau, Xingyu Jiang, George M. Whitesides§, Matthew J. Lang, Peter T. C. So||

    Molecular & Cellular Biomechanics, Vol.4, No.2, pp. 105-118, 2007, DOI:10.3970/mcb.2007.004.105

    Abstract During migration, asymmetrically polarized cells achieve motion by coordinating the protrusion and retraction of their leading and trailing edges, respectively. Although it is well known that local changes in the dynamics of actin cytoskeleton remodeling drive these processes, neither the cytoskeletal rheological properties of these migrating cells are well quantified nor is it understand how these rheological properties are regulated by underlying molecular processes. In this report, we have used soft lithography to create morphologically polarized cells in order to examine rheological differences between the front and rear zone of an NIH 3T3 cell posed for migration. In addition, we… More >

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