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The Cytoskeleton Under External Fluid Mechanical Forces: Hemodynamic Forces Acting on the Endothelium

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Abstract

The endothelium, a single layer of cells that lines all blood vessels, is the focus of intense interest in biomechanics because it is the principal recipient of hemodynamic shear stress. In arteries, shear stress has been demonstrated to regulate both acute vasoregulation and chronic adaptive vessel remodeling and is strongly implicated in the localization of atherosclerotic lesions. Thus, endothelial biomechanics and the associated mechanotransduction of shear stress are of great importance in vascular physiology and pathology. Here we discuss the important role of the cytoskeleton in a decentralization model of endothelial mechanotransduction. In particular, recent studies of four-dimensional cytoskeletal motion in living cells under external fluid mechanical forces are summarized together with new data on the spatial distribution of cytoskeletal strain. These quantitative studies strongly support the decentralized distribution of luminally imposed forces throughout the endo- thelial cell. © 2002 Biomedical Engineering Society.

PAC2002: 8717-d, 8717Aa, 8719Uv

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REFERENCES

  1. Ai, Z., A. Fischer, D. C. Spray, A. M. Brown, and G. I. Fishman. Wnt–1 regulation of connexin43 in cardiac myocytes. J. Clin. Invest. 105:161–171, 2000.

    Google Scholar 

  2. Ali, M. H., N. S. Chandel, C. E. Mathieu, and P. T. Schumacker. A novel mechanism of mechanotransduction: Role of mitochondria as transducers of cyclic strain. FASEB J. 14:A689, 2000.

    Google Scholar 

  3. Ballestrem, C., B. Wehrle–Haller, and B. A. Imhof. Actin dynamics in living mammalian cells. J. Cell. Sci. 111:1649–1658, 1998.

    Google Scholar 

  4. Barakat, A. I., E. V. Leaver, P. A. Pappone, and P. F. Davies. A flow–activated chloride–selective membrane current in vascular endothelial cells. Circ. Res. 85:820–828, 1999.

    Google Scholar 

  5. Barbee, K. A., P. F. Davies, and R. Lal. Subcellular distribution of shear stress at the surface of flow aligned and nonaligned endothelial monolayers. Am. J. Physiol. 268:H1765–H1772, 1995.

    Google Scholar 

  6. Burridge, K., and M. Chrzanowska–Wodnicka. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12:463–518, 1996.

    Google Scholar 

  7. Burridge, K., K. Fath, T. Kelly, G. Nuckolls, and C. Turner. Focal adhesions: Transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu. Rev. Cell Biol. 4:487–525, 1988.

    Google Scholar 

  8. Carminati, J. L., and T. Stearns. Microtubules orient the mitotic spindle in yeast through dynein–dependent interactions with the cell cortex. J. Cell Biol. 138:629–641, 1997.

    Google Scholar 

  9. Chalfie, M. Green fluorescent protein. Photochem. Photobiol. 62:651–656, 1995.

    Google Scholar 

  10. Chalfie, M., Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher. Green fluorescent protein as a marker for gene expression. Science 263:802–805, 1994.

    Google Scholar 

  11. Chen, K.–D., Y.–S. Li, M. Kim, S. Li, S. Yuan, S. Chien, and J. Y.–J. Shyy. Mechanotransduction in response to shear stress: Roles of receptor tyrosine kinases, integrins, and Shc. J. Biol. Chem. 274:18393–18400, 1999.

    Google Scholar 

  12. Choidas, A., A. Jungbluth, A. Sechi, J. Murphy, A. Ullrich, and G. Marriott. The suitability and application of a GFP–actin fusion protein for long–term imaging of the organization and dynamics of the cytoskeleton in mammalian cells. Eur. J. Cell Biol. 77:81–90, 1998.

    Google Scholar 

  13. Choquet, D., D. P. Felsenfeld, and M. P. Sheetz. Extracellular matrix rigidity causes strengthening of integrin–cytoskeleton linkages. Cell 88:39–48, 1997.

    Google Scholar 

  14. Cormack, B. Green fluorescent protein as a reporter of transcription and protein localization in fungi. Curr. Opin. Microbiol. 1:406–410, 1998.

    Google Scholar 

  15. Davies, P. F. Flow–mediated endothelial mechanotransduction. Physiol. Rev. 75:519–560, 1995.

    Google Scholar 

  16. Davies, P. F., K. A. Barbee, M. V. Volin, A. Robotewskyj, J. Chen, L. Joseph, M. L. Griem, M. N. Wernick, E. Jacobs, D. C. Polacek, N. DePaola, and A. I. Barakat. Spatial relationships in early signaling events of flow–mediated endothelial mechanotransduction. Annu. Rev. Physiol. 59:527–549, 1997.

    Google Scholar 

  17. Davies, P. F., A. Robotewskyj, and M. L. Griem. Quantitative studies of endothelial cell adhesion: Directional remodeling of focal adhesion sites in response to flow forces. J. Clin. Invest. 93:2031–2038, 1994.

    Google Scholar 

  18. Davies, P. F., and S. C. Tripathi. Mechanical stress mechanisms and the cell: An endothelial paradigm. Circ. Res. 72:239–245, 1993.

    Google Scholar 

  19. DePaola, N., P. F. Davies, W. F. Pritchard, Jr., L. Florez, N. Harbeck, and D. C. Polacek. Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. Proc. Natl. Acad. Sci. U.S.A. 96:3154–3159, 1999.

    Google Scholar 

  20. Dewey, Jr., C. F., S. R. Bussolari, M. A. Gimbrone, Jr., and P. F. Davies. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103:177–188, 1981.

    Google Scholar 

  21. Doyle, T., and D. Botstein. Movement of yeast cortical actin cytoskeleton visualized in vivo. Proc. Natl. Acad. Sci. U.S.A. 93:3886–3891, 1996.

    Google Scholar 

  22. Eckes, B., E. Colucci–Guyon, H. Smola, S. Nodder, C. Babinet, T. Krieg, and P. Martin. Impaired wound healing in embryonic and adult mice lacking vimentin. J. Cell. Sci. 113:2455–2462, 2000.

    Google Scholar 

  23. Eckes, B., D. Dogic, E. Colucci–Guyon, N. Wang, A. Maniotis, D. Ingber, A. Merckling, F. Langa, M. Aumailley, A. Delouvee, V. Koteliansky, C. Babinet, and T. Krieg. Impaired mechanical stability, migration and contractile capacity in vimentin–deficient fibroblasts. J. Cell. Sci. 111:1879–1907, 1998.

    Google Scholar 

  24. Errampalli, D., K. Leung, M. B. Cassidy, M. Kostrzynska, M. Blears, H. Lee, and J. T. Trevors. Applications of the green fluorescent protein as a molecular marker in environmental microorganisms. J. Microbiol. Methods 35:187–199, 1999.

    Google Scholar 

  25. Felsenfeld, D. P., D. Choquet, and M. P. Sheetz. Ligand binding regulates the directed movement of ß1 integrins on fibroblasts. Nature (London) 383:438–440, 1996.

    Google Scholar 

  26. Felsenfeld, D. P., P. L. Schwartzberg, A. Venegas, R. Tse, and M. P. Sheetz. Selective regulation of integrin–cytoskeleton interactions by the tyrosine kinase Src. Nat. Cell Biol. 1:200–206, 1999.

    Google Scholar 

  27. Feron, O., F. Saldana, J. B. Michel, and T. Michel. The endothelial nitric–oxide synthase–caveolin regulatory cycle. J. Biol. Chem. 273:3125–3128, 1998.

    Google Scholar 

  28. Fischer, M., S. Kaech, D. Knutti, and A. Matus. Rapid actin–based plasticity in dendritic spines. Neuron 20:847–854, 1998.

    Google Scholar 

  29. Fujimoto, T., A. Miyawaki, and K. Mikoshiba. Inositol 1,4,5–trisphosphate receptor–like protein in plasmalemmal caveolae is linked to actin filaments. J. Cell. Sci. 108:7–15, 1995.

    Google Scholar 

  30. Fung, Y. C., and S. Q. Liu. Elementary mechanics of the endothelium of blood vessels. J. Biomech. Eng. 115:1–12, 1993.

    Google Scholar 

  31. Galbraith, C. G., R. Skalak, and S. Chien. Shear stress induces spatial reorganization of the endothelial cell cytoskeleton. Cell Motil. Cytoskeleton 40:317–330, 1998.

    Google Scholar 

  32. Garcia–Cardena, G., R. Fan, D. F. Stern, J. Liu, and W. C. Sessa. Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin–1. J. Biol. Chem. 271:27237–27240, 1996.

    Google Scholar 

  33. Garcia–Cardena, G., P. Martasek, B. S. Masters, P. M. Skidd, J. Couet, S. Li, M. P. Lisanti, and W. C. Sessa. Dissecting the interaction between nitric oxide synthase NOS) and caveolin. Functional significance of the NOS caveolin binding domain in vivo. J. Biol. Chem. 272:25437–25440, 1997.

    Google Scholar 

  34. Goldman, R. D., Y. H. Chou, C. Dessev, G. Dessev, J. Eriksson, A. Goldman, S. Khuon, R. Kohnken, M. Lowy, R. Miller, K. Murphy, P. Opal, O. Skalli, and K. Straube. Dynamic aspects of cytoskeletal and karyoskeletal intermediate filament systems during the cell cycle. Cold Spring Harbor Symp. Quant. Biol. 56:629–642, 1991.

    Google Scholar 

  35. Goodwin, P. C. Wide–field deconvolution vs. confocal microscopy of living cells. Scanning 18:144–145, 1996.

    Google Scholar 

  36. Grieder, N. C., M. de Cuevas, and A. C. Spradling. The fusome organizes the microtubule network during oocyte differentiation in Drosophila. Development (Cambridge, U.K.) 127:4253–4264, 2000.

    Google Scholar 

  37. Gubin, A. N., B. Reddy, J. M. Njoroge, and J. L. Miller. Long–term, stable expression of green fluorescent protein in mammalian cells. Biochem. Biophys. Res. Commun. 236:347–350, 1997.

    Google Scholar 

  38. Gudi, S. R., C. B. Clark, and J. A. Frangos. Fluid flow rapidly activates G proteins in human endothelial cells. Circ. Res. 79:834–839, 1996.

    Google Scholar 

  39. Gudi, S. R., J. P. Nolan, and J. A. Frangos. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc. Natl. Acad. Sci. U.S.A. 95:2515–2519, 1998.

    Google Scholar 

  40. Guilak, F. Compression–induced changes in the shape and volume of the chondrocyte nucleus. J. Biomech. 28:1529–1541, 1995.

    Google Scholar 

  41. Haidekker, M. A., N. L'Heureux, and J. A. Frangos. Fluid shear stress increases membrane fluidity in endothelial cells. Am. J. Physiol. 278:H1401–H1406, 2000.

    Google Scholar 

  42. Heidemann, S. R., S. Kaech, R. E. Buxbaum, and A. Matus. Direct observations of the mechanical behaviors of the cytoskeleton in living fibroblasts. J. Cell Biol. 145:109–122, 1999.

    Google Scholar 

  43. Helmke, B. P., R. D. Goldman, and P. F. Davies. Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow. Circ. Res. 86:745–752, 2000.

    Google Scholar 

  44. Helmke, B. P., D. B. Thakker, R. D. Goldman, and P. F. Davies. Spatiotemporal analysis of flow–induced intermediate filament displacement in living endothelial cells. Biophys. J. 80:184–194, 2001.

    Google Scholar 

  45. Herrmann, H., and U. Aebi. Structure, assembly, and dynamics of intermediate filaments. Subcell Biochem. 31:319–362, 1998.

    Google Scholar 

  46. Hiraoka, Y., J. W. Sedat, and D. A. Agard. Determination of three–dimensional properties of a light microscope system: Partial confocal behavior in epifluorescence microscopy. Biophys. J. 57:325–333, 1990.

    Google Scholar 

  47. Ho, C.–L., J. L. Martys, A. Mikhailov, G. G. Gundersen, and R. K. H. Liem. Novel features of intermediate filament dynamics revealed by green fluroescent protein chimeras. J. Cell. Sci. 111:1767–1778, 1998.

    Google Scholar 

  48. Hoyer, J., R. Kohler, and A. Distler. Mechanosensitive Ca2+ oscillations and STOC activation in endothelial cells. FASEB J. 12:359–366, 1998.

    Google Scholar 

  49. Hynes, R. O. Integrins: Versatility, modulation, and signaling in cell adhesion. Cell 69:11–25, 1992.

    Google Scholar 

  50. Ingber, D. Integrins as mechanochemical transducers. Curr. Opin. Cell Biol. 3:841–848, 1991.

    Google Scholar 

  51. Ingber, D. Tensegrity: The architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59:575–599, 1997.

    Google Scholar 

  52. Inoue, N., S. Ramasamy, T. Fukai, R. M. Nerem, and D. G. Harrison. Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells. Circ. Res. 79:32–37, 1996.

    Google Scholar 

  53. Ishida, T., T. E. Peterson, N. L. Kovach, and B. C. Berk. MAP kinase activation by flow in endothelial cells. Role of ß1 integrins and tyrosine kinases. Circ. Res. 79:310–316, 1996.

    Google Scholar 

  54. Ishida, T., M. Takahashi, M. A. Corson, and B. C. Berk. Fluid shear stress–mediated signal transduction: How do endothelial cells transduce mechanical force into biological responses? Ann. N.Y. Acad. Sci. 811:12–23, 1997.

    Google Scholar 

  55. Ishide, N., M. Miura, M. Sakurai, and T. Takishima. Initiation and development of calcium waves in rat myocytes. Am. J. Physiol. 263:H327–H332, 1992.

    Google Scholar 

  56. Ishide, N., T. Urayama, K. Inoue, T. Komaru, and T. Takishima. Propagation and collision characteristics of calcium waves in rat myocytes. Am. J. Physiol. 259:H940–H950, 1990.

    Google Scholar 

  57. Jacobs,E. R., C. Cheliakine, D. Gebremedhin, P. F. Davies, and D. R. Harder. Shear activated channels in cell attached patches of vascular endothelial cells. Pflugers Arch.: Eur. J. Physiol. 431:129–131, 1995.

    Google Scholar 

  58. Janmey, P. A. The cytoskeleton and cell signaling: Component localization and mechanical coupling. Physiol. Rev. 78:763–781, 1998.

    Google Scholar 

  59. Janmey, P. A., U. Euteneuer, P. Traub, and M. Schliwa. Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J. Cell Biol. 113:155–160, 1991.

    Google Scholar 

  60. Janmey, P. A., U. Euteneuer, P. Traub, and M. Schliwa. Viscoelasticity of intermediate filament networks. Subcellular Biochemistry 31:381–397, 1998.

    Google Scholar 

  61. Ju, H., R. Zou, V. J. Venema, and R. C. Venema. Direct interaction of endothelial nitric–oxide synthase and caveolin–1 inhibits synthase activity. J. Biol. Chem. 272:18522–18525, 1997.

    Google Scholar 

  62. Kam, Z., M. O. Jones, H. Chen, D. A. Agard, and J. W. Sedat. Design and construction of an optimal illumination system for quantitative wide–field multi–dimensional microscopy. Bioimaging 1:71–81, 1993.

    Google Scholar 

  63. Kano, Y., K. Katoh, M. Masuda, and K. Fujiwara. Macromolecular composition of stress fiber–plasma membrane attachment sites in endothelial cells in situ. Circ. Res. 79:1000–1006, 1996.

    Google Scholar 

  64. Kimble, M., M. C. Kuzmiak, K. N. McGovern, and E. L. de Hostos. Microtubule organization and the effects of GFP–tubulin expression in Dictyostelium discoideum. Cell Motil. Cytoskeleton 47:48–62, 2000.

    Google Scholar 

  65. Ko, K., P. Arora, W. Lee, and C. McCulloch. Biochemical and functional characterization of intercellular adhesion and gap junctions in fibroblasts. Am. J. Physiol. 279:C147–C157, 2000.

    Google Scholar 

  66. Kohler, R., G. Schonfelder, H. Hopp, A. Distler, and J. Hoyer. Stretch–activated cation channel in human umbilical vein endothelium in normal pregnancy and in preeclampsia. J. Hypertens. 16:1149–1156, 1998.

    Google Scholar 

  67. Kowalczyk, A. P., P. Navarro, E. Dejana, E. A. Bornslaeger, K. J. Green, D. S. Kopp, and J. E. Borgwardt. VE–cadherin and desmoplakin are assembled into dermal microvascular endothelial intercellular junctions: A pivotal role for plakoglobin in the recruitment of desmoplakin to intercellular junctions. J. Cell. Sci. 111:3045–3057, 1998.

    Google Scholar 

  68. Levesque, M. J., and R. M. Nerem. The elongation and orientation of cultured endothelial cells in response to shear stress. J. Biomech. Eng. 107:341–347, 1985.

    Google Scholar 

  69. Li, S., B. P. Chen, N. Azuma, Y. L. Ju, S. Z. Wu, B. E. Sumpio, J. Y.–J. Shyy, and S. Chien. Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress. J. Clin. Invest. 103:1141–1150, 1999.

    Google Scholar 

  70. Li, S., M. Kim, Y. L. Hu, S. Jalali, D. D. Schlaepfer, T. Hunter, S. Chien, and J. Y.–J. Shyy. Fluid shear stress activation of focal adhesion kinase. Linking to mitogen–activated protein kinases. J. Biol. Chem. 272:30455–30462, 1997.

    Google Scholar 

  71. Ludin, B., and A. Matus. GFP illuminates the cytoskeleton. Trends Cell Biol. 8:72–77, 1998.

    Google Scholar 

  72. Malek, A. M., and S. Izumo. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J. Cell. Sci. 109:713–726, 1996.

    Google Scholar 

  73. Mallavarapu, A., K. Sawin, and T. Mitchison. A switch in microtubule dynamics at the onset of anaphase B in the mitotic spindle of Schizosaccharomyces pombe. Curr. Biol. 9:4123–1426, 1999.

    Google Scholar 

  74. Maniotis, A. J., C. S. Chen, and D. E. Ingber. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. U.S.A. 94:849–854, 1997.

    Google Scholar 

  75. Marchenko, S. M., and S. O. Sage. A novel mechanosensitive cationic channel from the endothelium of rat aorta. J. Physiol. (London) 498:419–425, 1997.

    Google Scholar 

  76. Margolin, W. Green fluorescent protein as a reporter for macromolecular localization in bacterial cells. Methods: A Companion to Methods in Enzymology 20:62–72, 2000.

    Google Scholar 

  77. Martys, J. L., C.–L. Ho, R. K. H. Liem, and G. G. Gundersen. Intermediate filaments in motion: observations of intermediate filaments in cells using green fluorescent proteinvimentin. Mol. Biol. Cell 10:1289–1295, 1999.

    Google Scholar 

  78. Nakache, M., and H. E. Gaub. Hydrodynamic hyperpolarization of endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 85:1841–1843, 1988.

    Google Scholar 

  79. Nerem, R. M., M. J. Levesque, and J. F. Cornhill. Vascular endothelial morphology as an indicator of the pattern of blood flow. J. Biomech. Eng. 103:172–176, 1981.

    Google Scholar 

  80. Noria, S., D. B. Cowan, A. I. Gotlieb, and B. L. Langille. Transient and steady–state effects of shear stress on endothelial cell adherens junctions. Circ. Res. 85:504–514, 1999.

    Google Scholar 

  81. Ochoa, G. C., V. I. Slepnev, L. Neff, N. Ringstad, K. Takei, L. Daniell, W. Kim, H. Cao, M. McNiven, R. Baron, and P. De Camilli. A functional link between dynamin and the actin cytoskeleton at podosomes. J. Cell Biol. 150:377–389, 2000.

    Google Scholar 

  82. Olesen, S.–P., D. E. Clapham, and P. F. Davies. Hemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature (London) 331:168–170, 1988.

    Google Scholar 

  83. Paemeleire, K., A. de Hemptinne, and L. Leybaert. Chemically, mechanically, and hyperosmolarity–induced calcium responses of rat cortical capillary endothelial cells in culture. Exp. Brain Res. 126:473–481, 1999.

    Google Scholar 

  84. Prahlad, V., M. Yoon, R. D. Moir, R. D. Vale, and R. D. Goldman. Rapid movements of vimentin on microtubule tracks: Kinesin–dependent assembly of intermediate filament networks. J. Cell Biol. 143:159–170, 1998.

    Google Scholar 

  85. Prasher, D. C., V. K. Eckenrode, W. W. Ward, F. G. Prendergast, and M. J. Cormier. Primary structure of the Aequorea Victoria green–fluorescent protein. Gene 111:229–233, 1992.

    Google Scholar 

  86. Pries, A. R., T. W. Secomb, and P. Gaehtgens. The endothelial surface layer. Pflugers Arch.: Eur. J. Physiol. 440:653–666, 2000.

    Google Scholar 

  87. Ren, X. D., W. B. Kiosses, and M. A. Schwartz. Regulation of the small GTP–binding protein Rho by cell adhesion and the cytoskeleton. EMBO J. 18:578–585, 1999.

    Google Scholar 

  88. Ren, X. D., W. B. Kiosses, D. J. Sieg, C. A. Otey, D. D. Schlaepfer, and M. A. Schwartz. Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J. Cell. Sci. 113:3673–3678, 2000.

    Google Scholar 

  89. Resnick, N., and M. A. Gimbrone, Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J. 9:874–882, 1995.

    Google Scholar 

  90. Rizzo, V., A. Sung, P. Oh, and J. E. Schnitzer. Rapid mechanotransduction in situ at the luminal cell surface of vascular endothelium and its caveolae. J. Biol. Chem. 273:26323–26329, 1998.

    Google Scholar 

  91. Robbins, J. R., A. I. Barth, H. Marquis, E. L. de Hostos, W. J. Nelson, and J. A. Theriot. Listeria monocytogenes exploits normal host cell processes to spread from cell to cell. J. Cell. Biol. 146:1333–1350, 1999.

    Google Scholar 

  92. Schiffers, P. M., D. Henrion, C. M. Boulanger, E. Colucci–Guyon, F. Langa–Vuves, H. van Essen, G. E. Fazzi, B. I. Levy, and J. G. De Mey. Altered flow–induced arterial remodeling in vimentin–deficient mice. J. Arterioscler., Thromb., Vasc. Biol. 20:611–616, 2000.

    Google Scholar 

  93. Schliwa, M., and J. van Blerkom. Structural interaction of cytoskeletal components. J. Cell Biol. 90:222–235, 1981.

    Google Scholar 

  94. Shah, J. V., L. Z. Wang, P. Traub, and P. A. Janmey. Interaction of vimentin with actin and phospholipids. Biol. Bull. 194:402–405, 1998.

    Google Scholar 

  95. Steinert, P. M., Y. H. Chou, V. Prahlad, D. A. Parry, L. N. Marekov, K. C. Wu, S. I. Jang, and R. D. Goldman. A high molecular weight intermediate filament–associated protein in BHK–21 cells is nestin, a type VI intermediate filament protein. J. Biol. Chem. 274:9881–9890, 1999.

    Google Scholar 

  96. Straub, S. V., D. R. Giovannucci, and D. I. Yule. Calcium wave propagation in pancreatic acinar cells: Functional interaction of inositol 1,4,5–trisphosphate receptors, ryanodine receptors, and mitochondria. J. Gen. Physiol. 116:547–560, 2000.

    Google Scholar 

  97. Svitkina, T. M., A. B. Verkhovsky, and G. G. Borisy. Plectin sidearms mediate interaction of intermediate filaments with microtubules and other components of the cytoskeleton. J. Cell Biol. 135:991–1007, 1996.

    Google Scholar 

  98. Takahashi, M., and B. C. Berk. Mitogen–activated protein kinase (ERK1/2) activation by shear stress and adhesion in endothelial cells. Essential role for a herbimycin–sensitive kinase. J. Clin. Invest. 98:2623–2631, 1996.

    Google Scholar 

  99. Tsien, R. Y. The green fluorescent protein. Annu. Rev. Biochem. 67:509–544, 1998.

    Google Scholar 

  100. Verkhusha, V. V., S. Tsukita, and H. Oda. Actin dynamics in lamellipodia of migrating border cells in the Drosophila ovary revealed by a GFP–actin fusion protein. FEBS Lett. 445:395–401, 1999.

    Google Scholar 

  101. Vikstrom, K. L., S.–S. Lim, R. D. Goldman, and G. G. Borisy. Steady state dynamics of intermediate filaments networks. J. Cell Biol. 118:121–129, 1992.

    Google Scholar 

  102. Wang, N. Mechanical interactions among cytoskeletal filaments. Hypertension 32:162–165, 1998.

    Google Scholar 

  103. Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127, 1993.

    Google Scholar 

  104. Wang, S. S., and S. H. Thompson. Local positive feedback by calcium in the propagation of intracellular calcium waves. Biophys. J. 69:1683–1697, 1995.

    Google Scholar 

  105. Wei, Z., K. Costa, A. B. Al–Mehdi, C. Dodia, V. Muzykantov, and A. B. Fisher. Simulated ischemia in flow–adapted endothelial cells leads to generation of reactive oxygen species and cell signaling. Circ. Res. 85:682–689, 1999.

    Google Scholar 

  106. Wernick, M. N., M. L. Griem, A. Robotewskyj, and P. F. Davies. Image analysis of the dynamic changes of adhesion sites in endothelial cells subjected to directional flow in vitro. J. Vasc. Invest. 4:15–23, 1998.

    Google Scholar 

  107. Westphal, M. N., A. Jungbluth, M. Heidecker, B. Muhlbauer, C. Heizer, J. M. Schwartz, G. Marriott, and G. Gerisch. Microfilament dynamics during cell movement and chemotaxis monitored using a GFP–actin fusion protein. Curr. Biol. 7:176–183, 1997.

    Google Scholar 

  108. Wu, Z., K. Wong, M. Glogauer, R. P. Ellen, and C. A. McCulloch. Regulation of stretch–activated intracellular calcium transients by actin filaments. Biochem. Biophys. Res. Commun. 261:419–425, 1999.

    Google Scholar 

  109. Yoon, M., R. D. Moir, V. Prahlad, and R. D. Goldman. Motile properties of vimentin intermediate filament networks in living cells. J. Cell Biol. 143:147–157, 1998.

    Google Scholar 

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  1. Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA

    Brian P. Helmke

  2. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA

    Brian P. Helmke & Peter F. Davies

  3. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA

    Peter F. Davies

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Helmke, B.P., Davies, P.F. The Cytoskeleton Under External Fluid Mechanical Forces: Hemodynamic Forces Acting on the Endothelium. Annals of Biomedical Engineering 30, 284–296 (2002). https://doi.org/10.1114/1.1467926

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