Vascular Cell Physiology Under Shear Flow: Role of Cell Mechanics and Mechanotransduction

  • Devon Scott
  • Wei Tan
  • Jerry S. H. Lee
  • Owen J. T. McCarty
  • Monica T. Hinds
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 12)


Whether examined at the micro- or macroscale, biological phenomenona are not exempt from physical laws and principles. The vasculature is frequently utilized as a model system to better understand and analyze the consequences of biophysical forces on biochemical processes and ultimate biological phenotypes. Given the complexities of biological systems, there is an inherent need to focus in order to properly elucidate mechanisms. Mechanotransduction and cell mechanics in various stages of angiogenesis have long been examined at distinct length-scales ranging from subcellular, cellular, multi-cellular, tissue, and beyond. This chapter will highlight research over the past decades that have contributed to revealing the importance and interplay between biophysical forces (compressive and shear flow) and biological behavior (motility, regulation of smooth muscle cells, polarity). Abnormal biophysical forces, such as hypertension, contribute significantly to vascular diseases, including atherosclerosis and aneurysm formation. Understanding the relationship between biophysical forces and biological behavior is required to understand the mechanisms of vascular disease.


Pulmonary Hypertension Pulse Pressure Focal Adhesion Arterial Stiffness Pulsatile Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the American Heart Association 09BGIA2260384 (M.T.H), and the National Institute of Health grants 1R01HL103728 (M.T.H.), R01HL101972 (O.J.T.M.) and 1U54CA143906 (O.J.T.M.).


  1. 1.
    Berne, R.M., Levy, M.N.: Cardiovascular Physiology. Mosby Year Book Inc, St. Louis (1992)Google Scholar
  2. 2.
    Wang, Y.X.: Do measures of vescular compliance correlate with endothelial function? Curr. Diab. Rep. 7, 265–268 (2007)CrossRefGoogle Scholar
  3. 3.
    Ganoug W.: Review of Medical Physiology, vol. 22. The McGraw-Hill, NY (2005)Google Scholar
  4. 4.
    Sherwood, L.: Human Physiology. Brooks/Cole, Belmont (2004)Google Scholar
  5. 5.
    Nichols, W.W., Edwards, D.G.: Arterial elastance and wave reflection augmentation of systolic blood pressure: Deleterious effects and implications for therapy. J. Cardiovasc. Pharmacol. Ther. 6, 5–21 (2001)Google Scholar
  6. 6.
    Vlachopoulos, C., Aznaouridis, K., Stefanadis, C.: Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece, Heart, 92, 1544–1550 (2006)Google Scholar
  7. 7.
    Michell, G.F.: Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. Physiol. Aging Vasculature 105, 1652–1660 (2008)Google Scholar
  8. 8.
    Chemla, D., Hebert, J.L., Coirault, C., Zamani, K., Suard, I., Colin, P., Lecarpentier, Y.: Total arterial compliance estimated by stroke volume-to-aortic pulse pressure ratio in humans. AJP 274, H500–H505 (1998)Google Scholar
  9. 9.
    Safar M.E., Levy, B., Struijker-Boudier, H.: Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Cirulation 107, 2864–2869 (2003)Google Scholar
  10. 10.
    Mitchell, J.G.F., Conlin, P.R., Dunlap, M.E., Lacourcière, Y., Arnold, J.M.O., gilvie, R.I.O., Neutel, J., Izzo, J.L.: Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension 51, 105 (2008)Google Scholar
  11. 11.
    Nichols, W.W., O’Rourke, M.F.: McDonlald’s Blood Flow in Arteries. Oxford University Press Inc, New York (2005)Google Scholar
  12. 12.
    O’Rourke, M.: Arterial stiffness, systolic blood pressusre and logical treatment of hypertension. Hypertension 15, 339–347 (1990)CrossRefGoogle Scholar
  13. 13.
    Glasser, S.P., Arnett, D.K., McVeigh, G.E., Finkelstein, S.M., Bank, A.J., Morgan, D.J., Cohn, J.N.: Vascular compliance and cardiovascular disease. AJH 10, 1175–1189 (1997)Google Scholar
  14. 14.
    Greenwald, S.E.: Ageing of the conduit arteries. J. Pathol. 211, 157–172 (2007)CrossRefGoogle Scholar
  15. 15.
    Safar, M.E.: Peripheral pulse pressure, large arteries, and microvessels. Hypertension 44, 121–122 (2004)CrossRefGoogle Scholar
  16. 16.
    Safar, M., Levy, B.I., Struijkeer-Boudier, H.: Current perspectives on arterial stiffness and pulse pressure in hypertnesion and cardiovascular diseases. Circulation 107, 2864–2869 (2003)Google Scholar
  17. 17.
    Ku, D.N.: Blood flow in arteries. Ann. Rev. Fluid Mech. 29 (1997)Google Scholar
  18. 18.
    Streeter, V.L., Keitzer, W.F., Bohr, D.F.: Pulsatile pressure and flow through distensible vessels. Circ. Res. 13, 3–20 (1963)Google Scholar
  19. 19.
    Capell, B.C., Collins, F.S.: Human laminopathies: nuclei gone genetically awry. Nat. Rev. Genet. 7, 940–952 (2006)Google Scholar
  20. 20.
    Makous, N., Friedman, S., Yakovac, V., Maris, E.P.: Cardiovascular manifestations in progeria. Report of clinical and pathologic findings in a patient with severe arterisclerotic heart disease and aortic stenosis. Am. Heart J. 64, 334–346 (1962)Google Scholar
  21. 21.
    Baker, P.B., Baba, N., Boesel, C.P.: Cardiovascular abnormalities in progeria. Case report and review of the literature. Arch. Pathol. Lab. Med. 105, 384–386 (1981)Google Scholar
  22. 22.
    Zhang, Y., Dunn, M.L., Drexler, E.S., McCowan, C.N., Slifka, A.J., Ivy, D.D., Shandas, R.: A microsctructal hyperelastic model of pulmonary arteries under normo- and hypertensive conditions. Ann. Biomed. Eng. 33, 1042–1052 (2005)Google Scholar
  23. 23.
    Lammers, K.P., Qi, J., Hunter, K., Lanning, C., Albietz, J., Hofmeister, S., Mecham, R., Stenmark, K., Shandas, R.: Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves. Am. J. Physiol. Heart Circ. Physiol. 295, 1451–1459 (2008)Google Scholar
  24. 24.
    Fung, Y.C.: Biomechanics Circulation. Springer, New York (1997)CrossRefGoogle Scholar
  25. 25.
    O’Rourke, M.F., Safar, M.E.: Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 46, 200–204 (2005)CrossRefGoogle Scholar
  26. 26.
    Feihl, L.L., Waeber, B.: The macrocirculation and microciculation of hypertension. Current Hypertension Reports 11, 182–189 (2009)Google Scholar
  27. 27.
    Safer, M.E., Struijker-Boudier, H.A.: Cross-talk between macro- and microcirculation. Acta Physiol. 198, 417–430 (2010)CrossRefGoogle Scholar
  28. 28.
    Intengan, S.E., Schiffrin, H.D.: Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension 36, 312–318 (2000)CrossRefGoogle Scholar
  29. 29.
    Murphy, L.M.: Mayo Clinic Cardiology, 3rd edn. Mayo Clinic Scientific Press, Rochester (2007)Google Scholar
  30. 30.
    Stenmark, K.R., McMurtry, I.F.: Vascular remodeling versus vasoconstriction in chronic hypoxic pulmonary hypertension a time for reappraisal. Circ. Res. 97, 95–98 (2005)CrossRefGoogle Scholar
  31. 31.
    Aaronson, P., Robertson, T.P., Knock, G.A., Becker, S., Lewis, T.H., Snetkov, V., Ward, J.P.T.: Hypoxic pulmonary vasoconstriction: mechanisms and controversies. J. Physiol. 270, 53–58 (2006)CrossRefGoogle Scholar
  32. 32.
    Sweeney, M., Yuan, J.X.J.: Hypoxic pulmonary vasoconstriction: role of voltage-gated potassium channels. Respir. Res. 1, 40–48 (2000)CrossRefGoogle Scholar
  33. 33.
    Morrell, A.S., Archer, S.L., Dupuis, J., Jones, P.L., MacLean, M.R., McMutry, I.F., Stenmark, K.R., Thistlethwaite, P.A., Weissmann, N., Yuan, J.X.J., Weir, E.K.: Cellular and molecuar basis of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 54, S20–S31 (2009)Google Scholar
  34. 34.
    Sanchez, O., Marcos, E., Perros, F., Fadel, E., Tu, L., Humbert, M., Dartevelle, P., Simonneau, G., Adnot, S., Eddahibi, S.: Role of endothelium-derived CC Chemokine Ligand 2 in idioplathic pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 176, 1041–1047 (2007)Google Scholar
  35. 35.
    Veyssier-Belot, C., Cacoub, P.: Role of the endothelial and smooth muscle cells in physiophathogy and treatment management of pulmonary hypertension. Cardio. Res., 44, 274–282 (1999)Google Scholar
  36. 36.
    Owens, G.K., Rabinovitch, P.S., Schwartz, S.M.: Smooth muscle cell hypertrophy versus hyperplasia in hypertnesion. Proc. Natl. Acad. Sci. 78, 7759–7763 (1981)CrossRefGoogle Scholar
  37. 37.
    Quinn, S.M.T.P., Soifer, S.J., Gutierrez, J.A.: Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L897–L903 (2002)Google Scholar
  38. 38.
    Lehoux, S., Tedgui, A.: Cellular mechanics and gene expression in blood vessels. J. Biomech. 36, 631–643 (2003)Google Scholar
  39. 39.
    Reneman, R.S., Arts, T., Hoeks, A.P.G.: Wall shear stress- an important determinant of endothelial cell function and structure- in the arterial system in vivo. J. Vasc. Res. 43, 251–269 (2006)Google Scholar
  40. 40.
    Albuquerque, W.C.M.L.C., Savla, U., Schnaper, H.W., Flozak, A.S.: Shear stress enhances human endothelial cell wound closure in vitro. Am. J. Physiol. Heart Circ. Physiol. 279, H293–H302 (2000)Google Scholar
  41. 41.
    Traub, O., Berk, B.C.: Laminar shear stress: mechanisms by which endothelial cells transduce an arthoprotective force. Arterioscler. Thromb. Vasc. Biol. 18, 667–685 (1998)CrossRefGoogle Scholar
  42. 42.
    Li, M., Stenmark, K.R., Shandas, R., Tan, W.: Effects of pathological flow on pulmonary artery endothelial production of vasoactive mediators and growth factors. J. Vasc. Res. 46, 561–571 (2009)Google Scholar
  43. 43.
    O’Rourke, M.F., Hashimoto, J.: Mechanical factors in arterial aging: A clinical perspective. JACC 50, 1–13 (2007)Google Scholar
  44. 44.
    Safar, M.E., Lacolley, P.: Disturbance of maro- and microcirculations : relations with pulse pressure and cardiac organ damage. Am. J. Physiol. Heart Circ. Physiol. 293, H1–H7 (2007)CrossRefGoogle Scholar
  45. 45.
    Pyke, K.E., Tschakovsky, M.E.: The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J. Physiol. 568(2), 357–369 (2005)CrossRefGoogle Scholar
  46. 46.
    Budhiraja, R., Tuder, R.M., Hassoun, P.M.: Endothelial dysfunction in pulmonary hypertension. Circulation 109, 159–165 (2004)CrossRefGoogle Scholar
  47. 47.
    Vanhoutte, P.M., Feletou, M., Taddei, S.: Endothelium-dependent contractions in hypertension. Brithish J. Pharmacol 144, 449–458 (2005)Google Scholar
  48. 48.
    Giaid, A., Saleh, D.: Reduced expression of endothelial ntric oxide synthase in the lungs of patients with pulmonary hypertension. N. Engl. J. Med. 333, 214–221 (1995)CrossRefGoogle Scholar
  49. 49.
    Abranham, W., Raynolds, M.V., Gottschall, B., Badesch, D.B., Wynne, K.M., Groves, B.M., Lowes, B.D., Bristow, M.R., Perryman, B., Voelkel, N.F.: Importance of angiotensin-converting enzyme in pulmonary hypertension. Cardiology 86, 9–15 (1995)CrossRefGoogle Scholar
  50. 50.
    Du, L., Sullivan, D.C.: Signaling molecules in nonfamililial pulmonary hypertension. N. Engl. J. Med. 348, 500–509 (2003)CrossRefGoogle Scholar
  51. 51.
    Humbert, M., Morrell, N.W., Archer, S.L., Stenmark, K.R., MacLean, M.R., Lang, I.M., Christman, B.W., Weir, E.K., Eickelberg, O., Voelkel, N.F., Rabinovitch, M.: Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 43, S13–S24 (2004)CrossRefGoogle Scholar
  52. 52.
    Barakat, A.I.: Responsiveness of vascular endothelium to shear stress: potential role of ion channels and cellular cytoskeleton (review). Int. J. Mol. Med. 4, 323–332 (1999)Google Scholar
  53. 53.
    Ingber, D.E.: Tensegrity: the architectural basis of cellular mechanotransduction. Annu. Rev. Physiol. 59, 575–599 (1997)CrossRefGoogle Scholar
  54. 54.
    Helmke, B.P.: Molecular control of cytoskeletal mechanics by hemodynamic forces. Physiology (Bethesda) 20, 43–53 (2005)CrossRefGoogle Scholar
  55. 55.
    Helmke, B.P., Davies, P.F.: The cytoskeleton under external fluid mechanical forces: hemodynamic forces acting on the endothelium. Ann. Biomed. Eng. 30, 284–296 (2002)CrossRefGoogle Scholar
  56. 56.
    Tzima, E., Del Pozo, M.A., Kiosses, W.B., Mohamed, S.A., Li, S., Chien, S., Schwartz, M.A.: Activation of Racl by shear stress in endothelial cells mediates both cytoskeletal reorganization and effects on gene expression. EMBO J. 21, 6791–6800 (2002)CrossRefGoogle Scholar
  57. 57.
    Vojciak-Stothard, B., Ridley, A.J.: Shear stress-induced endothelial cell polarization is mediated by Rho and Rac but not Cdc42 or PI 3-kinases. J. Cell Biol. 161, 429–439 (2003)CrossRefGoogle Scholar
  58. 58.
    del Alamo, J.C., Norwich, G.N., Li, Y.S., Lasheras, J.C., Chien, S.: Anisotropic rhelogy and directional mechanotransduction in vascular endothelial cells. Proc. Nat. Aca. 105, 15411–15416 (2008)CrossRefGoogle Scholar
  59. 59.
    Lee, J.S., Panorchan, P., Hale, C.M., Khatau, S.B., Kole, T.P., Tseng, Y., Wirtz, D.: Ballistic intracellular nanoreheology reveals ROCK-hard cytoplasmic stiffening response to fluid flow. J. Cell Sci. 119, 1760–1768 (2006)CrossRefGoogle Scholar
  60. 60.
    Davies, P.F., Robotewskyj, A., Griem, M.L.: Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. J. Clin. Invest. 93, 2031–2038 (1994)CrossRefGoogle Scholar
  61. 61.
    Uttayarat, P., Toworfe, G.K., Dietrich, F., Lelkes, P.I., Composto, R.J.: Topographic guidance of endothelial cells on silicone surfaces with micro- to nanogrooves: orientation of actin filaments and focal adhesions. J. Biomed. Mater. Res. A 75, 668–680 (2005)CrossRefGoogle Scholar
  62. 62.
    Lehoux, S., Castier, Y., Tedgui, A.: Molecular mechanisms of the vascular responses to haemodynamic forces. J. Intern. Med. 259, 381–392 (2006)CrossRefGoogle Scholar
  63. 63.
    Langille, B.L.: Morphologic responses of endothelium to shear stress: reorganization of the adherens junction. Microcirculation 8, 195–206 (2001)Google Scholar
  64. 64.
    Miao, H., Hu, Y.L., Shiu, Y.T., Yuan, S., Zhao, Y., Kaunas, R., Wang, Y., Jin, G., Usami, S., Chien, S.: Effects of flow patterns on the localization and expression of VE-cadherin at vascular endothelial cell junctions: in vivo and in vitro investigations. J. Vasc. Res. 42, 77–89 (2005)CrossRefGoogle Scholar
  65. 65.
    Gray, D.S., Liu, W.F., Shen, C.J., Bhadriraju, K., Nelson, C.M., Chen, C.S.: Engineering amount of cell–cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton. Exp. Cell Res. 314, 2846–2854 (2008)CrossRefGoogle Scholar
  66. 66.
    Vartanian, K.B., Kirkpatrick, S.J., Hanson, S.R., Hinds, M.T.: Endothelial cell cytoskeletal alignment independent of fluid shear stress on micropatterned surfaces. Biochem. Biophys. Res. Commun. 371, 787–792 (2008)CrossRefGoogle Scholar
  67. 67.
    Alenghat, F.J., Ingber, D.E.: Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins. Sci. STKE 2002, PE6 (2002)Google Scholar
  68. 68.
    Hale, C.M., Shrestha, A.L., Khatau, S.B., Stewart-Hutchinson P.J., Hernandes, L., Stewart C.L., Hodzic D., Wirtz, D.: Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models. Biophys. J. 95(11), 5462–5475 (2008)Google Scholar
  69. 69.
    Hennekam, R.C.: Hutchinson-Gilford progeria syndrome: review of the phenotype. Am. J. Med. Genet. 23, 2603–2624 (2006)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Devon Scott
    • 1
  • Wei Tan
    • 2
  • Jerry S. H. Lee
    • 3
    • 4
  • Owen J. T. McCarty
    • 1
  • Monica T. Hinds
    • 1
  1. 1.Department of Biomedical EngineeringOregon Health and Science UniversityPortlandUSA
  2. 2.Department of Mechanical EngineeringUniversity of Colorado at BoulderBoulderUSA
  3. 3.Department of Chemical and Biomolecular EngineeringJohns Hopkins UniversityBaltimoreUSA
  4. 4.Center for Strategic Scientific InitiativesNational Cancer InstituteBethesdaUSA

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