Annals of Biomedical Engineering

, Volume 33, Issue 12, pp 1719–1723 | Cite as

Cellular Fluid Mechanics and Mechanotransduction

  • John M. Tarbell
  • Sheldon Weinbaum
  • Roger D. Kamm


Mechanotransduction, the transformation of an applied mechanical force into a cellular biomolecular response, is briefly reviewed focusing on fluid shear stress and endothelial cells. Particular emphasis is placed on recent studies of the surface proteoglycan layer (glycocalyx) as a primary sensor of fluid shear stress that can transmit force to apical structures such as the plasma membrane or the actin cortical web where transduction can take place or to more remote regions of the cell such as intercellular junctions and basal adhesion plaques where transduction can also occur. All of these possibilities are reviewed from an integrated perspective.


Shear stress Endothelial cells Mechanotransduction Glycocalyx Cytoskeleton 


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  1. 1.
    Adamson, R. H., and G. Clough. Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. J. Physiol. 445:473–486, 1992.Google Scholar
  2. 2.
    Bao, G. Mechanics of biomolecules. J. Mech. Phys. Solids 50:2237–2274, 2002.MathSciNetMATHGoogle Scholar
  3. 3.
    Butler, P. J., T. C. Tsou, J. Y. Li, S. Usami, and S. Chien. Rate sensitivity of shear-induced changes in the lateral diffusion of endothelial cell membrane lipids: A role for membrane perturbation in shear-induced MAPK activation. FASEB J. 16:216–218, 2002.Google Scholar
  4. 4.
    Caro, C. G., and R. M. Nerem. Transport of 14C-4-cholesterol between serum and wall in the perfused dog common carotid artery. Circ. Res. 32:187–205, 1973.Google Scholar
  5. 5.
    Chen, C. S., J. Tan, and J. Tien. Mechanotransduction at cell–matrix and cell–cell contacts. Annu. Rev. Biomed. Eng. 6:275–302, 2004.CrossRefGoogle Scholar
  6. 6.
    Chen, K. D., Y. S. Li, M. Kim, S. Li, S. Yuan, S. Chien, and J. Y. Shyy. Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J. Biol. Chem. 274:18393–18400, 1999.Google Scholar
  7. 7.
    Constantinescu, A. A., H. Vink, and J. A. Spaan. Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL. Am. J. Physiol. 280:H1051–H1057, 2001.Google Scholar
  8. 8.
    Damiano, E. R. The effect of the endothelial glycocalyx on the motion of red blood cells through capillaries. Microvasc. Res. 55:77–91, 1998.CrossRefGoogle Scholar
  9. 9.
    Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75:519–560, 1995.Google Scholar
  10. 10.
    Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75:519–560, 1995.Google Scholar
  11. 11.
    Dewey, C. F., S. R. Bussolari, M. A. Gimbrone, P. F. Davies. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103:177–185, 1981.CrossRefGoogle Scholar
  12. 12.
    Drenckhahn, D., and W. Ness. The endothelial contractile cytoskeleton. In: Vascular Endothelium: Physiology, Pathology, and Therapeutic Opportunities. New Horizon Series 3:1–25 (Schattauer, Stuttgart) 1997.Google Scholar
  13. 13.
    Feng, J. Weinbaum S. Lubrication theory in highly compressible porous media: The mechanics of skiing, from red cells to humans. J. Fluid. Mech. 422:281–317, 2000.CrossRefMathSciNetMATHGoogle Scholar
  14. 14.
    Florian, J. A., J. R. Kosky, K. Ainslie, Z. Pang, R. O. Dull, and J. M. Tarbell. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ. Res. 93:e136–e142, 2003.CrossRefGoogle Scholar
  15. 15.
    Fry, D. L. Hemodynamic forces in atherogenesis. In: Cerebrovascular Diseases, edited by P Scheinberg. Raven Press, 1976, pp. 77–95.Google Scholar
  16. 16.
    Geiger, B., and A. Bershadsky. Exploring the neighborhood: Adhesion-coupled cell mechanosensors. Cell 110:139–142, 2002.CrossRefGoogle Scholar
  17. 17.
    Haidekker, M. A., N. L'Heureux, and J. A. Frangos. Fluid shear stress increases membrane fluidity in endothelial cells: A study with DCVJ fluorescence. Am. J. Physiol. Heart Circ. Physiol. 278:H1401–H1406, 2000.Google Scholar
  18. 18.
    Hamill, O. P., and B. Martinac. Molecular basis of mechanotransduction in living cells. Physiol. Rev. 81:685–740, 2001.Google Scholar
  19. 19.
    Hecker, M., A. Mulsch, E. Bassenge, and R. Busse. Vasoconstriction and increased flow: Two principal mechanisms of shear stress-dependent endothelial autocoid release. Am. J. Physiol. 265:H828–H833, 1993.Google Scholar
  20. 20.
    Henry, C. B., and B. R. Duling. Permeation of the luminal capillary glycocalyx is determined by hyaluronan. Am. J. Physiol. 277:H508–H514, 1999.Google Scholar
  21. 21.
    Hu, S., J. Chen, B. Fabry, Y. Numaguchi, A. Gouldstone, D. E. Ingber, J. J. Fredberg, J. P. Butler, and N. Wang. Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am. J. Physiol. Cell Physiol. 285:C1082–C1090, 2003.Google Scholar
  22. 22.
    Ingber, D. E. Cellular basis of mechanotransduction. Biol. Bull. 194:323–325; Discussion 325–327, 1998.Google Scholar
  23. 23.
    Kamm, R. D., and M. R. Kaazempur-Mofrad. On the molecular basis for mechanotransduction, Mech. Chem. Biosyst. 1(4) MCB online (, 2004.
  24. 24.
    Karcher, H., J. Lammerding, H. Huang, R. T. Lee, R. D. Kamm, and M. R. Kaazempur-Mofrad. A three-dimensional viscoelastic model for cell deformation with experimental verification. Biophys. J. 85:3336–3349, 2003.CrossRefGoogle Scholar
  25. 25.
    Lehoux, S., and A. Tedgui. Cellular mechanics and gene expression in blood vessels. J. Biomech. 36:631–643, 2003.CrossRefGoogle Scholar
  26. 26.
    Luft, J. H. Fine structure of capillary and endocapillary layer as revealed by ruthenium red. Fed. Proc. 25:1773–1783, 1966.Google Scholar
  27. 27.
    Mack, P. J., M. R. Kaazempur-Mofrad, H. Karcher, R. T. Lee, and R. D. Kamm. Force-induced focal adhesion translocation: Effects of force amplitude and frequency. Am. J. Physiol. Cell Physiol. 287:C954–C962, 2004.CrossRefGoogle Scholar
  28. 28.
    Mochizuki, S., H. Vink, O. Hiramatsu, T. Kajita, F. Shigeto, J. Spaan, and F. Kajiya. Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release. Am. J. Physiol. 285:H722–H726, 2003.Google Scholar
  29. 29.
    Mulivor, A. W., and H. H. Lipowsky. Role of glycocalyx in leukocyte-endothelial cell adhesion. Am. J. Physiol. 283:H1282–H1291, 2002.Google Scholar
  30. 30.
    Norvell, S. M., S. M. Ponik, D. K. Bowen, R. Gerard, and F. M. Pavalko. Fluid shear stress induction of COX-2 protein and prostaglandin release in cultured MC3T3-E1 osteoblasts does not require intact microfilaments or microtubules. J. Appl. Physiol. 96:957–966, 2004.Google Scholar
  31. 31.
    Odde, D. J., L. Ma, A. H. Briggs, A. DeMarco, and M. W. Kirschner. Microtubule bending and breaking in living fibroblasts. J. Cell Sci. 112(Pt 19):3283–3288, 1999.Google Scholar
  32. 32.
    Pohl, U., K. Herlan, A. Huang, and E. Bassenge. EDRF-mediated shear-induced dilation opposes myogenic vasoconstriction in small rabbit arteries. Am. J. Physiol. 261: H2106–H2113, 1991.Google Scholar
  33. 33.
    Pries, A. R., T. W. Secomb, and P. Gaehtgens. The endothelial surface layer. Eur. J. Physiol. 440:653–666, 2000.CrossRefGoogle Scholar
  34. 34.
    Riveline, D., E. Zamir, N. Q. Balaban, U. S. Schwarz, T. Ishizaki, S. Narumiya, Z. Kam, B. Geiger, and A. D. Bershadsky. Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153:1175–1186, 2001.CrossRefGoogle Scholar
  35. 35.
    Sawada, Y., and M. P. Sheetz. Force transduction by Triton cytoskeletons. J. Cell Biol. 156:609–615, 2002.CrossRefGoogle Scholar
  36. 36.
    Schnittler, H. J., S. W. Schneider, H. Raifer, F. Luo, P. Dieterich, I. Just, and K. Aktories. Role of actin filaments in endothelial cell-cell adhesion and membrane stability under fluid shear stress. Pflugers Arch. 442:675–687, 2001.CrossRefGoogle Scholar
  37. 37.
    Secomb, T. W., R. Hsu, and A. R. Pries. Effect of the endothelial surface layer on transmission of fluid shear stress to endothelial cells. Biorheology 38:143–150, 2001.Google Scholar
  38. 38.
    Squire, J. M., M. Chew, G. Nneji, C. Neal, J. Barry, and C. Michel. Quasi-periodic substructure in the microvessel endothelial glycocalyx: A possible explanation for molecular filtering? J. Struct. Biol. 136:239–255, 2001.CrossRefGoogle Scholar
  39. 39.
    Tarbell, J. M. Mass transport in arteries and the localization of atherosclerosis. Annu. Rev. Biomed. Eng. 5:79–118, 2003.CrossRefGoogle Scholar
  40. 40.
    Thi, M. M., J. M. Tarbell, S. Weinbaum, and D. C. Spray. The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper car” model. Proc. Natl. Acad. Sci. U.S.A. 101:16483–16485, 2004.CrossRefGoogle Scholar
  41. 41.
    Tschumperlin, D. J. EGRF autocrine signaling in a compliant interstitial space: Mechanotransduction from the outside-in. Cell Cycle 3:996–997, 2004.Google Scholar
  42. 42.
    van den Berg, B. M., H. Vink, and J. A. Spaan. The endothelial glycocalyx protects against myocardial edema. Circ. Res. 92:e592–e594, 2003.CrossRefGoogle Scholar
  43. 43.
    Vink, H., A. A. Constantinescu, and J. A. Spaan. Oxidized lipoproteins degrade the endothelial surface layer: Implications for platelet-endothelial cell adhesion. Circulation 101:1500–1502, 2000.Google Scholar
  44. 44.
    Weinbaum, S., X. Zhang, Y. Han, H. Vink, and S. C. Cowin. Mechanotransduction and flow across the endothelial glycocalyx. Proc. Natl. Acad. Sci. U.S.A. 100:7988–7995, 2003.CrossRefGoogle Scholar
  45. 45.
    Zamir, E., and B. Geiger. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114:3583–3590, 2001.Google Scholar

Copyright information

© Biomedical Engineering Society 2005

Authors and Affiliations

  • John M. Tarbell
    • 1
    • 3
  • Sheldon Weinbaum
    • 1
  • Roger D. Kamm
    • 2
  1. 1.Department of Biomedical EngineeringCity College of New YorkNew York
  2. 2.Departments of Mechanical and Biological EngineeringMassachusetts Institute of TechnologyCambridge
  3. 3.Department of Biomedical EngineeringCity College of New YorkNew York

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