Biorheology - Volume 38, issue 2-3

Article Type: Other

Citation: Biorheology, vol. 38, no. 2-3, pp. 69-69, 2001

Article Type: Other

Citation: Biorheology, vol. 38, no. 2-3, pp. 71-74, 2001

Authors: Huang, Wei | Sher, Yuh‐Pyng | Peck, Konan | Fung, Yuan Cheng

Article Type: Research Article

Abstract: Microarray gene chip technology is a powerful invention looking for applications. A general principle is proposed here to direct the power of the technology toward physiology, medicine, and pharmacology. Our principle is to match quantitative measures of gene expression with the trend of mathematical parameters that describe biological functions. Mathematical parameterization is the heart. The procedure is illustrated by lung physiology, including the hypoxic hypertension, rheological properties of the tissues, and the remodeling of the pulmonary arterial wall under hypertensive stress. We show first how to reduce the experimental results on these physiological functions into mathematical formulas, and how the …parameters of these formulas describe the functional trends precisely. Then under the assumption that the microarray reveals gene activities quantitatively, we match the trends of the gene activity with the trends of the functional parameters. Genes whose trends do match are interpreted as relevant to the functions. Those that do not match are considered irrelevant to the functions. The more functions we consider, the fewer will be the number of genes that are relevant to all functions. Thus we learn about the generality and specificity of the influence of genes on physiology. Show more

Keywords: cDNA microarray, gene expression, mechanical properties, morphometry, opening angle, wall thickness

Citation: Biorheology, vol. 38, no. 2-3, pp. 75-87, 2001

Authors: Willeke, Thomas | Scharffetter‐Kochanek, Karin | Gaehtgens, Peter | Walzog, Barbara

Article Type: Research Article

Abstract: During the recruitment of human polymorphonuclear neutrophils (PMN) to sites of inflammation, leukocyte adhesion molecules of the β2 integrin (CD11/CD18) family mediate firm adhesion of these cells to the endothelial cell monolayer lining the vessel wall. This process is a prerequisite for shape change and spreading of PMN on the endothelium which eventually allows PMN emigration into the extravascular space. In order to elucidate the molecular mechanisms which mediate this sequence of events, intracellular protein tyrosine signaling was studied subsequent to β2 integrin‐mediated ligand binding. Using western blotting technique, β2 integrin‐mediated adhesion was found to induce tyrosine …phosphorylation of different proteins. The effect was absent in PMN derived from CD18‐deficient mice which lack any β2 integrin expression on the cell surface demonstrating the specificity of the observed response. Inhibition of β2 integrin‐mediated tyrosine signaling by herbimycin A almost completely inhibited adhesion, shape change, and subsequent spreading of PMN. Herbimycin A also diminished chemotactic migration of these cells in response to the soluble mediator N‐formyl‐Met–Leu–Phe (fMLP). In contrast, treatment of PMN with cytochalasin D had no substantial effect on β2 integrin‐mediated signaling or adhesion but inhibited shape change, spreading, and chemotactic migration of PMN. This suggests that the signaling capacity exerted by β2 integrins upon ligand binding was independent of an intact cytoskeleton. Moreover, the β2 integrin‐mediated activation of intracellular signal transduction pathways was critical for firm adhesion of PMN, the prerequisite subsequent shape change and spreading, which allows emigration of PMN into the extravascular space. Show more

Keywords: Adhesion, host defence, inflammation, PMN, emigration

Citation: Biorheology, vol. 38, no. 2-3, pp. 89-100, 2001

Authors: Li, Song | Bhatia, Sangeeta | Hu, Ying‐Li | Shiu, Yan‐Ting | Li, Yi‐Shuan | Usami, Shunichi | Chien, Shu

Article Type: Research Article

Abstract: The migration of vascular endothelial cells (ECs) plays an important role in vascular remodeling. Here we studied the effects of cell morphology on the migration of bovine aortic ECs by culturing cells on micropatterned strips of collagen matrix (60‐, 30‐, and 15‐μm wide). The spreading areas of the cells on 15‐ and 30‐μm wide strips were 30% lower than those on 60‐ μm wide strips and unpatterned collagen. The cells on 15‐μm wide strips completely aligned in the direction of the strip, and had significantly lower shape index than those in all other groups. On strips of all widths, ECs …tended to migrate in the direction of strips. ECs on 15‐μm wide strips had highest speed, particularly in the direction of the strip. Vinculin staining showed that the leading edge of ECs on 15‐μm wide strips had focal adhesions that were oriented with their lamellipodial protrusion and the direction of cell migration; this arrangement of the focal adhesions may promote EC migration. The present study provides direct evidence on the role of cell morphology in EC migration, and will help us to understand the mechanisms of EC migration during angiogenesis and wound healing. Show more

Keywords: Cell morphology, endothelial cell migration, extracellular matrix, micropattern

Citation: Biorheology, vol. 38, no. 2-3, pp. 101-108, 2001

Authors: Shyy, John Y.‐J.

Article Type: Research Article

Abstract: Shear stresses play an important role in vascular biology in health and disease. While disturbed flows with low shear stresses in the bends and bifurcations of the arterial tree are atherogenic, laminar flows with high shear stresses in the straight part of the vessel is atheroresistant. Thus, elucidation of the mechanotransduction mechanism in vascular endothelial cells in response to shear stress has become an important research topic among bioengineers and vascular biologists. Here is a summary of studies performed in Dr. Shu Chien's laboratory on shear stress‐induced signal transduction and gene expression during the period from 1992–1999. These studies, together …with efforts from other research groups, demonstrate that integrins, which are transmembrane molecules that interact with both extracellular matrices and intracellular cytoskeleton and kinases in the focal adhesions, are important in mechanotransduction. This hypothesis is mainly supported by the similarity between cellular and molecular events elicited by shear stress and those activated during the integrin‐mediated cell attachment to extracellular matrices. Evidence is also provided to show that the dynamic and specific interaction between integrin and extracellular matrices is essential for mechanotransduction. Show more

Keywords: Integrin, extracellular matrix, cytoskeleton, shear stress, MCP‐1 gene

Citation: Biorheology, vol. 38, no. 2-3, pp. 109-117, 2001

Authors: Weinbaum, Sheldon | Guo, Peng | You, Lidan

Article Type: Research Article

Abstract: In this paper we shall describe new mechanical models for the deformation of the actin filament bundles in kidney microvilli and osteocytic cell processes to see whether these cellular extensions, like the stereocilia on hair cells in the inner ear, can function as mechanotransducers when subject to physiological flow. In the case of kidney microvilli we show that the hydrodynamic drag forces at the microvilli tip are <0.01 pN, but there is a 38‐fold force amplification on the actin filaments at the base of the microvilli due to the resisting moment in its terminal web. This leads to forces that …are more than sufficient to deform the terminal web complex of the microvillus where ezrin has been shown to couple the actin cytoskeleton to the Na+ /H+ exchanger. In the case of bone cell processes we show that the actin filament bundles have an effective Young's modulus that is 200 times > the measured modulus for the actin gel in the cell body. It is, therefore, unlikely that bone cell processes respond in vivo to fluid shear stress, as proposed in [59]. However, we show that the fluid drag forces on the pericellular matrix which tethers the cell processes to the canalicular wall can produce a 20–100 fold amplification of bone tissue strains in the actin filament bundle of the cell process. Show more

Keywords: Mechanotransduction, brush border microvilli, osteocytic cell processes, glomerulotubular balance, bone strain amplification

Citation: Biorheology, vol. 38, no. 2-3, pp. 119-142, 2001

Authors: Secomb, T.W. | Hsu, R. | Pries, A.R.

Article Type: Research Article

Abstract: Responses of vascular endothelial cells to mechanical shear stresses resulting from blood flow are involved in regulation of blood flow, in structural adaptation of vessels, and in vascular disease. Interior surfaces of blood vessels are lined with a layer of bound or adsorbed macromolecules, known as the endothelial surface layer (ESL). In vivo investigations have shown that this layer has a width of order 1 μm, that it substantially impedes plasma flow, and that it excludes flowing red blood cells. Here, the effect of the ESL on transmission of shear stress to endothelial cells is examined using a theoretical model. …The layer is assumed to consist of a matrix of molecular chains extending from the surface, held in tension by a slight increase in colloid osmotic pressure relative to that in free‐flowing plasma. It is shown that, under physiological conditions, shear stress is transmitted to the endothelial surface almost entirely by the matrix, and fluid shear stresses on endothelial cell membranes are very small. Rapid fluctuations in shear stress are strongly attenuated by the layer. The ESL may therefore play an important role in sensing of shear stress by endothelial cells. Show more

Keywords: Endothelium, glycocalyx, mechanotransduction, shear stress

Citation: Biorheology, vol. 38, no. 2-3, pp. 143-150, 2001

Authors: Melder, Robert J. | Kristensen, Claus A. | Munn, Lance L. | Jain, Rakesh K.

Article Type: Research Article

Abstract: The delivery of cells to specific regions of the vasculature is a critical step in many therapeutic strategies. These include the packaging of DNA or RNA in cell “vehicles” for delivery to tissues, the reconstitution of differentiated cells to an organ using embryonic stem cells, and the enhancement of the immune response using effector lymphocytes. In most cases, these cells must be injected systemically. Unfortunately, ex vivo manipulation or activation can affect cell visco‐elastic properties, making it difficult for the injected cells to traverse capillary beds. Compounding the problem is the fact that common agents used in the laboratory for …increasing cell deformability generally have adverse side effects on the therapeutic potential of the cells. Using micropipet aspiration techniques, cytotoxicity assays and in vivo trafficking studies we show that: (1) the rigidity of injected effector cells directly affects resistance to passage through tissue; (2) modulation of cytoskeletal organization can be used to decrease cell rigidity, but can also compromise therapeutic efficacy; and (3) thioglycollate, an agent which does not influence effector lymphocyte cytotoxic activity, reduces cell rigidity and entrapment in the lungs. Show more

Keywords: Activated lymphocyte, rigidity, deformability, thioglycollate

Citation: Biorheology, vol. 38, no. 2-3, pp. 151-159, 2001

Authors: Kwon, Soon Yong | Lin, Tong | Takei, Hiroshi | Ma, Qingjin | Wood, Douglas J. | O'Connor, Daniel | Sung, K.‐L. Paul

Article Type: Research Article

Abstract: Total joint replacement prostheses are required to withstand corrosive environments and sustain millions of loading and articulation cycles during their term of implantation. Wear debris generation has been implicated as one of the primary causes of periprosthetic osteolysis and subsequent implant loosening in total joint replacements. Particulate debris consisting of metals, polyethylene, ceramics, and bone cement have each been shown to provoke a biological response in joint tissues. The major cell types within the interfacial granulomatous fibrous tissues consist of fibroblasts, macrophages, lymphocytes, and foreign‐body giant cells. Osteoblasts are one of the principal cell types in the bone tissue adjacent …to prostheses, maintaining physiologic bone remodeling through the balanced coordination of bone formation and resorption in concert with osteoclasts. To date the phenomenon of osteoblast phagocytosis of titanium particles has been suggested, but has not been sufficiently studied or confirmed. This study seeks to clarify the influence of titanium particles on osteoblast adhesion, deformability, proliferation, and gene expression profile. These studies were accomplished by performing biorheological testing, Northern blot analysis and RNase protection assay. The uptake of metallic particles by the osteoblast resulted in a particle–filament complex formation, which induced a series of variations in cell function. Understanding these variations is critical to expanding our knowledge of implant loosening and elucidating the nature of prosthetic joint failure. This study suggests that the impact of titanium particles on osteoblast function and subsequent implant loosening may have been previously underestimated. Show more

Keywords: Osteoblast, particle, adhesion, deformation, proliferation, gene expression

Citation: Biorheology, vol. 38, no. 2-3, pp. 161-183, 2001