Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 2002 Aug;83(2):858–879. doi: 10.1016/S0006-3495(02)75214-4

Determination of cellular strains by combined atomic force microscopy and finite element modeling.

Guillaume T Charras 1, Mike A Horton 1
PMCID: PMC1302192  PMID: 12124270

Abstract

Many organs adapt to their mechanical environment as a result of physiological change or disease. Cells are both the detectors and effectors of this process. Though many studies have been performed in vitro to investigate the mechanisms of detection and adaptation to mechanical strains, the cellular strains remain unknown and results from different stimulation techniques cannot be compared. By combining experimental determination of cell profiles and elasticities by atomic force microscopy with finite element modeling and computational fluid dynamics, we report the cellular strain distributions exerted by common whole-cell straining techniques and from micromanipulation techniques, hence enabling their comparison. Using data from our own analyses and experiments performed by others, we examine the threshold of activation for different signal transduction processes and the strain components that they may detect. We show that modulating cell elasticity, by increasing the F-actin content of the cytoskeleton, or cellular Poisson ratio are good strategies to resist fluid shear or hydrostatic pressure. We report that stray fluid flow in some substrate-stretch systems elicits significant cellular strains. In conclusion, this technique shows promise in furthering our understanding of the interplay among mechanical forces, strain detection, gene expression, and cellular adaptation in physiology and disease.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. A-Hassan E., Heinz W. F., Antonik M. D., D'Costa N. P., Nageswaran S., Schoenenberger C. A., Hoh J. H. Relative microelastic mapping of living cells by atomic force microscopy. Biophys J. 1998 Mar;74(3):1564–1578. doi: 10.1016/S0006-3495(98)77868-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ajubi N. E., Klein-Nulend J., Alblas M. J., Burger E. H., Nijweide P. J. Signal transduction pathways involved in fluid flow-induced PGE2 production by cultured osteocytes. Am J Physiol. 1999 Jan;276(1 Pt 1):E171–E178. doi: 10.1152/ajpendo.1999.276.1.E171. [DOI] [PubMed] [Google Scholar]
  3. Banes A. J., Tsuzaki M., Yamamoto J., Fischer T., Brigman B., Brown T., Miller L. Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol. 1995 Jul-Aug;73(7-8):349–365. doi: 10.1139/o95-043. [DOI] [PubMed] [Google Scholar]
  4. Barbee K. A., Mundel T., Lal R., Davies P. F. Subcellular distribution of shear stress at the surface of flow-aligned and nonaligned endothelial monolayers. Am J Physiol. 1995 Apr;268(4 Pt 2):H1765–H1772. doi: 10.1152/ajpheart.1995.268.4.H1765. [DOI] [PubMed] [Google Scholar]
  5. Brown T. D., Bottlang M., Pedersen D. R., Banes A. J. Loading paradigms--intentional and unintentional--for cell culture mechanostimulus. Am J Med Sci. 1998 Sep;316(3):162–168. doi: 10.1097/00000441-199809000-00003. [DOI] [PubMed] [Google Scholar]
  6. Butler P. J., Norwich G., Weinbaum S., Chien S. Shear stress induces a time- and position-dependent increase in endothelial cell membrane fluidity. Am J Physiol Cell Physiol. 2001 Apr;280(4):C962–C969. doi: 10.1152/ajpcell.2001.280.4.C962. [DOI] [PubMed] [Google Scholar]
  7. Caille N., Tardy Y., Meister J. J. Assessment of strain field in endothelial cells subjected to uniaxial deformation of their substrate. Ann Biomed Eng. 1998 May-Jun;26(3):409–416. doi: 10.1114/1.132. [DOI] [PubMed] [Google Scholar]
  8. Charras G. T., Lehenkari P. P., Horton M. A. Atomic force microscopy can be used to mechanically stimulate osteoblasts and evaluate cellular strain distributions. Ultramicroscopy. 2001 Jan;86(1-2):85–95. doi: 10.1016/s0304-3991(00)00076-0. [DOI] [PubMed] [Google Scholar]
  9. Charras Guillaume T., Horton Mike A. Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation. Biophys J. 2002 Jun;82(6):2970–2981. doi: 10.1016/S0006-3495(02)75638-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen J., Fabry B., Schiffrin E. L., Wang N. Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells. Am J Physiol Cell Physiol. 2001 Jun;280(6):C1475–C1484. doi: 10.1152/ajpcell.2001.280.6.C1475. [DOI] [PubMed] [Google Scholar]
  11. Diamond S. L., Sachs F., Sigurdson W. J. Mechanically induced calcium mobilization in cultured endothelial cells is dependent on actin and phospholipase. Arterioscler Thromb. 1994 Dec;14(12):2000–2006. doi: 10.1161/01.atv.14.12.2000. [DOI] [PubMed] [Google Scholar]
  12. Drury J. L., Dembo M. Hydrodynamics of micropipette aspiration. Biophys J. 1999 Jan;76(1 Pt 1):110–128. doi: 10.1016/S0006-3495(99)77183-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fermor B., Gundle R., Evans M., Emerton M., Pocock A., Murray D. Primary human osteoblast proliferation and prostaglandin E2 release in response to mechanical strain in vitro. Bone. 1998 Jun;22(6):637–643. doi: 10.1016/s8756-3282(98)00047-7. [DOI] [PubMed] [Google Scholar]
  14. Girard P. R., Nerem R. M. Endothelial cell signaling and cytoskeletal changes in response to shear stress. Front Med Biol Eng. 1993;5(1):31–36. [PubMed] [Google Scholar]
  15. Glogauer M., Arora P., Yao G., Sokholov I., Ferrier J., McCulloch C. A. Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching. J Cell Sci. 1997 Jan;110(Pt 1):11–21. doi: 10.1242/jcs.110.1.11. [DOI] [PubMed] [Google Scholar]
  16. Glogauer M., Ferrier J. A new method for application of force to cells via ferric oxide beads. Pflugers Arch. 1998 Jan;435(2):320–327. doi: 10.1007/s004240050518. [DOI] [PubMed] [Google Scholar]
  17. Glogauer M., Ferrier J., McCulloch C. A. Magnetic fields applied to collagen-coated ferric oxide beads induce stretch-activated Ca2+ flux in fibroblasts. Am J Physiol. 1995 Nov;269(5 Pt 1):C1093–C1104. doi: 10.1152/ajpcell.1995.269.5.C1093. [DOI] [PubMed] [Google Scholar]
  18. Gu W. Y., Lai W. M., Mow V. C. A triphasic analysis of negative osmotic flows through charged hydrated soft tissues. J Biomech. 1997 Jan;30(1):71–78. doi: 10.1016/s0021-9290(96)00099-1. [DOI] [PubMed] [Google Scholar]
  19. Gudi S., Nolan J. P., Frangos J. A. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2515–2519. doi: 10.1073/pnas.95.5.2515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Guilak F., Mow V. C. The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage. J Biomech. 2000 Dec;33(12):1663–1673. [PubMed] [Google Scholar]
  21. Guilak F. Volume and surface area measurement of viable chondrocytes in situ using geometric modelling of serial confocal sections. J Microsc. 1994 Mar;173(Pt 3):245–256. doi: 10.1111/j.1365-2818.1994.tb03447.x. [DOI] [PubMed] [Google Scholar]
  22. Hansen J. C., Skalak R., Chien S., Hoger A. An elastic network model based on the structure of the red blood cell membrane skeleton. Biophys J. 1996 Jan;70(1):146–166. doi: 10.1016/S0006-3495(96)79556-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Haskin C., Cameron I., Athanasiou K. Physiological levels of hydrostatic pressure alter morphology and organization of cytoskeletal and adhesion proteins in MG-63 osteosarcoma cells. Biochem Cell Biol. 1993 Jan-Feb;71(1-2):27–35. doi: 10.1139/o93-005. [DOI] [PubMed] [Google Scholar]
  24. Hayakawa K., Sato N., Obinata T. Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp Cell Res. 2001 Aug 1;268(1):104–114. doi: 10.1006/excr.2001.5270. [DOI] [PubMed] [Google Scholar]
  25. Hu H., Sachs F. Mechanically activated currents in chick heart cells. J Membr Biol. 1996 Dec;154(3):205–216. doi: 10.1007/s002329900145. [DOI] [PubMed] [Google Scholar]
  26. Hung C. T., Allen F. D., Pollack S. R., Brighton C. T. Intracellular Ca2+ stores and extracellular Ca2+ are required in the real-time Ca2+ response of bone cells experiencing fluid flow. J Biomech. 1996 Nov;29(11):1411–1417. doi: 10.1016/0021-9290(96)84536-2. [DOI] [PubMed] [Google Scholar]
  27. Ingber D. E. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J Cell Sci. 1993 Mar;104(Pt 3):613–627. doi: 10.1242/jcs.104.3.613. [DOI] [PubMed] [Google Scholar]
  28. Jortikka M. O., Parkkinen J. J., Inkinen R. I., Kärner J., Järveläinen H. T., Nelimarkka L. O., Tammi M. I., Lammi M. J. The role of microtubules in the regulation of proteoglycan synthesis in chondrocytes under hydrostatic pressure. Arch Biochem Biophys. 2000 Feb 15;374(2):172–180. doi: 10.1006/abbi.1999.1543. [DOI] [PubMed] [Google Scholar]
  29. Ko K. S., Arora P. D., McCulloch C. A. Cadherins mediate intercellular mechanical signaling in fibroblasts by activation of stretch-sensitive calcium-permeable channels. J Biol Chem. 2001 Jul 20;276(38):35967–35977. doi: 10.1074/jbc.M104106200. [DOI] [PubMed] [Google Scholar]
  30. Ko K. S., McCulloch C. A. Partners in protection: interdependence of cytoskeleton and plasma membrane in adaptations to applied forces. J Membr Biol. 2000 Mar 15;174(2):85–95. doi: 10.1007/s002320001034. [DOI] [PubMed] [Google Scholar]
  31. Lee H. S., Millward-Sadler S. J., Wright M. O., Nuki G., Salter D. M. Integrin and mechanosensitive ion channel-dependent tyrosine phosphorylation of focal adhesion proteins and beta-catenin in human articular chondrocytes after mechanical stimulation. J Bone Miner Res. 2000 Aug;15(8):1501–1509. doi: 10.1359/jbmr.2000.15.8.1501. [DOI] [PubMed] [Google Scholar]
  32. Lehenkari P. P., Charras G. T., Nykänen A., Horton M. A. Adapting atomic force microscopy for cell biology. Ultramicroscopy. 2000 Feb;82(1-4):289–295. doi: 10.1016/s0304-3991(99)00138-2. [DOI] [PubMed] [Google Scholar]
  33. Long Q., Xu X. Y., Ramnarine K. V., Hoskins P. Numerical investigation of physiologically realistic pulsatile flow through arterial stenosis. J Biomech. 2001 Oct;34(10):1229–1242. doi: 10.1016/s0021-9290(01)00100-2. [DOI] [PubMed] [Google Scholar]
  34. Malek A. M., Izumo S. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J Cell Sci. 1996 Apr;109(Pt 4):713–726. doi: 10.1242/jcs.109.4.713. [DOI] [PubMed] [Google Scholar]
  35. Maniotis A. J., Chen C. S., Ingber D. E. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):849–854. doi: 10.1073/pnas.94.3.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Marotti G., Ferretti M., Muglia M. A., Palumbo C., Palazzini S. A quantitative evaluation of osteoblast-osteocyte relationships on growing endosteal surface of rabbit tibiae. Bone. 1992;13(5):363–368. doi: 10.1016/8756-3282(92)90452-3. [DOI] [PubMed] [Google Scholar]
  37. McAllister T. N., Frangos J. A. Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways. J Bone Miner Res. 1999 Jun;14(6):930–936. doi: 10.1359/jbmr.1999.14.6.930. [DOI] [PubMed] [Google Scholar]
  38. McCreadie BARBARA RIEMER, Hollister SCOTT J. Strain Concentrations Surrounding an Ellipsoid Model of Lacunae and Osteocytes. Comput Methods Biomech Biomed Engin. 1997;1(1):61–68. doi: 10.1080/01495739708936695. [DOI] [PubMed] [Google Scholar]
  39. Mente P. L., Lewis J. L. Experimental method for the measurement of the elastic modulus of trabecular bone tissue. J Orthop Res. 1989;7(3):456–461. doi: 10.1002/jor.1100070320. [DOI] [PubMed] [Google Scholar]
  40. Nesbitt S. A., Horton M. A. Trafficking of matrix collagens through bone-resorbing osteoclasts. Science. 1997 Apr 11;276(5310):266–269. doi: 10.1126/science.276.5310.266. [DOI] [PubMed] [Google Scholar]
  41. Niggel J., Sigurdson W., Sachs F. Mechanically induced calcium movements in astrocytes, bovine aortic endothelial cells and C6 glioma cells. J Membr Biol. 2000 Mar 15;174(2):121–134. doi: 10.1007/s002320001037. [DOI] [PubMed] [Google Scholar]
  42. Owan I., Burr D. B., Turner C. H., Qiu J., Tu Y., Onyia J. E., Duncan R. L. Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. Am J Physiol. 1997 Sep;273(3 Pt 1):C810–C815. doi: 10.1152/ajpcell.1997.273.3.C810. [DOI] [PubMed] [Google Scholar]
  43. Parkkinen J. J., Lammi M. J., Inkinen R., Jortikka M., Tammi M., Virtanen I., Helminen H. J. Influence of short-term hydrostatic pressure on organization of stress fibers in cultured chondrocytes. J Orthop Res. 1995 Jul;13(4):495–502. doi: 10.1002/jor.1100130404. [DOI] [PubMed] [Google Scholar]
  44. Peake M. A., Cooling L. M., Magnay J. L., Thomas P. B., El Haj A. J. Selected contribution: regulatory pathways involved in mechanical induction of c-fos gene expression in bone cells. J Appl Physiol (1985) 2000 Dec;89(6):2498–2507. doi: 10.1152/jappl.2000.89.6.2498. [DOI] [PubMed] [Google Scholar]
  45. Picart C., Dalhaimer P., Discher D. E. Actin protofilament orientation in deformation of the erythrocyte membrane skeleton. Biophys J. 2000 Dec;79(6):2987–3000. doi: 10.1016/S0006-3495(00)76535-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Radmacher M. Measuring the elastic properties of biological samples with the AFM. IEEE Eng Med Biol Mag. 1997 Mar-Apr;16(2):47–57. doi: 10.1109/51.582176. [DOI] [PubMed] [Google Scholar]
  47. Rawlinson S. C., Pitsillides A. A., Lanyon L. E. Involvement of different ion channels in osteoblasts' and osteocytes' early responses to mechanical strain. Bone. 1996 Dec;19(6):609–614. doi: 10.1016/s8756-3282(96)00260-8. [DOI] [PubMed] [Google Scholar]
  48. Rawlinson S. C., Wheeler-Jones C. P., Lanyon L. E. Arachidonic acid for loading induced prostacyclin and prostaglandin E(2) release from osteoblasts and osteocytes is derived from the activities of different forms of phospholipase A(2). Bone. 2000 Aug;27(2):241–247. doi: 10.1016/s8756-3282(00)00323-9. [DOI] [PubMed] [Google Scholar]
  49. Reich K. M., McAllister T. N., Gudi S., Frangos J. A. Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts. Endocrinology. 1997 Mar;138(3):1014–1018. doi: 10.1210/endo.138.3.4999. [DOI] [PubMed] [Google Scholar]
  50. Rosales O. R., Isales C. M., Barrett P. Q., Brophy C., Sumpio B. E. Exposure of endothelial cells to cyclic strain induces elevations of cytosolic Ca2+ concentration through mobilization of intracellular and extracellular pools. Biochem J. 1997 Sep 1;326(Pt 2):385–392. doi: 10.1042/bj3260385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rubin C. T., Lanyon L. E. Regulation of bone formation by applied dynamic loads. J Bone Joint Surg Am. 1984 Mar;66(3):397–402. [PubMed] [Google Scholar]
  52. Russell B., Motlagh D., Ashley W. W. Form follows function: how muscle shape is regulated by work. J Appl Physiol (1985) 2000 Mar;88(3):1127–1132. doi: 10.1152/jappl.2000.88.3.1127. [DOI] [PubMed] [Google Scholar]
  53. Ryder K. D., Duncan R. L. Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels. J Bone Miner Res. 2001 Feb;16(2):240–248. doi: 10.1359/jbmr.2001.16.2.240. [DOI] [PubMed] [Google Scholar]
  54. Sachs F., Morris C. E. Mechanosensitive ion channels in nonspecialized cells. Rev Physiol Biochem Pharmacol. 1998;132:1–77. doi: 10.1007/BFb0004985. [DOI] [PubMed] [Google Scholar]
  55. Sakai K., Mohtai M., Iwamoto Y. Fluid shear stress increases transforming growth factor beta 1 expression in human osteoblast-like cells: modulation by cation channel blockades. Calcif Tissue Int. 1998 Dec;63(6):515–520. doi: 10.1007/s002239900567. [DOI] [PubMed] [Google Scholar]
  56. Salter D. M., Robb J. E., Wright M. O. Electrophysiological responses of human bone cells to mechanical stimulation: evidence for specific integrin function in mechanotransduction. J Bone Miner Res. 1997 Jul;12(7):1133–1141. doi: 10.1359/jbmr.1997.12.7.1133. [DOI] [PubMed] [Google Scholar]
  57. Sato M., Nagayama K., Kataoka N., Sasaki M., Hane K. Local mechanical properties measured by atomic force microscopy for cultured bovine endothelial cells exposed to shear stress. J Biomech. 2000 Jan;33(1):127–135. doi: 10.1016/s0021-9290(99)00178-5. [DOI] [PubMed] [Google Scholar]
  58. Schaffer J. L., Rizen M., L'Italien G. J., Benbrahim A., Megerman J., Gerstenfeld L. C., Gray M. L. Device for the application of a dynamic biaxially uniform and isotropic strain to a flexible cell culture membrane. J Orthop Res. 1994 Sep;12(5):709–719. doi: 10.1002/jor.1100120514. [DOI] [PubMed] [Google Scholar]
  59. Simon B. R., Kaufmann M. V., McAfee M. A., Baldwin A. L. Finite element models for arterial wall mechanics. J Biomech Eng. 1993 Nov;115(4B):489–496. doi: 10.1115/1.2895529. [DOI] [PubMed] [Google Scholar]
  60. Stamenović D., Fredberg J. J., Wang N., Butler J. P., Ingber D. E. A microstructural approach to cytoskeletal mechanics based on tensegrity. J Theor Biol. 1996 Jul 21;181(2):125–136. doi: 10.1006/jtbi.1996.0120. [DOI] [PubMed] [Google Scholar]
  61. Suchyna T. M., Johnson J. H., Hamer K., Leykam J. F., Gage D. A., Clemo H. F., Baumgarten C. M., Sachs F. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol. 2000 May;115(5):583–598. doi: 10.1085/jgp.115.5.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tagawa H., Wang N., Narishige T., Ingber D. E., Zile M. R., Cooper G., 4th Cytoskeletal mechanics in pressure-overload cardiac hypertrophy. Circ Res. 1997 Feb;80(2):281–289. doi: 10.1161/01.res.80.2.281. [DOI] [PubMed] [Google Scholar]
  63. Van Rietbergen B., Müller R., Ulrich D., Rüegsegger P., Huiskes R. Tissue stresses and strain in trabeculae of a canine proximal femur can be quantified from computer reconstructions. J Biomech. 1999 Apr;32(4):443–451. doi: 10.1016/s0021-9290(99)00024-x. [DOI] [PubMed] [Google Scholar]
  64. Wang N., Ingber D. E. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys J. 1994 Jun;66(6):2181–2189. doi: 10.1016/S0006-3495(94)81014-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Weinbaum S., Cowin S. C., Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. 1994 Mar;27(3):339–360. doi: 10.1016/0021-9290(94)90010-8. [DOI] [PubMed] [Google Scholar]
  66. Wozniak M., Fausto A., Carron C. P., Meyer D. M., Hruska K. A. Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression. J Bone Miner Res. 2000 Sep;15(9):1731–1745. doi: 10.1359/jbmr.2000.15.9.1731. [DOI] [PubMed] [Google Scholar]
  67. Wu H. W., Kuhn T., Moy V. T. Mechanical properties of L929 cells measured by atomic force microscopy: effects of anticytoskeletal drugs and membrane crosslinking. Scanning. 1998 Aug;20(5):389–397. doi: 10.1002/sca.1998.4950200504. [DOI] [PubMed] [Google Scholar]
  68. Wu J. Z., Herzog W. Finite element simulation of location- and time-dependent mechanical behavior of chondrocytes in unconfined compression tests. Ann Biomed Eng. 2000 Mar;28(3):318–330. doi: 10.1114/1.271. [DOI] [PubMed] [Google Scholar]
  69. Xia S. L., Ferrier J. Propagation of a calcium pulse between osteoblastic cells. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1212–1219. doi: 10.1016/s0006-291x(05)81535-9. [DOI] [PubMed] [Google Scholar]
  70. Xu Q. Biomechanical-stress-induced signaling and gene expression in the development of arteriosclerosis. Trends Cardiovasc Med. 2000 Jan;10(1):35–41. doi: 10.1016/s1050-1738(00)00042-6. [DOI] [PubMed] [Google Scholar]
  71. Yellowley C. E., Jacobs C. R., Donahue H. J. Mechanisms contributing to fluid-flow-induced Ca2+ mobilization in articular chondrocytes. J Cell Physiol. 1999 Sep;180(3):402–408. doi: 10.1002/(SICI)1097-4652(199909)180:3<402::AID-JCP11>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  72. You J., Reilly G. C., Zhen X., Yellowley C. E., Chen Q., Donahue H. J., Jacobs C. R. Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 osteoblasts. J Biol Chem. 2001 Jan 26;276(16):13365–13371. doi: 10.1074/jbc.M009846200. [DOI] [PubMed] [Google Scholar]
  73. You J., Yellowley C. E., Donahue H. J., Zhang Y., Chen Q., Jacobs C. R. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. J Biomech Eng. 2000 Aug;122(4):387–393. doi: 10.1115/1.1287161. [DOI] [PubMed] [Google Scholar]
  74. Zaman G., Suswillo R. F., Cheng M. Z., Tavares I. A., Lanyon L. E. Early responses to dynamic strain change and prostaglandins in bone-derived cells in culture. J Bone Miner Res. 1997 May;12(5):769–777. doi: 10.1359/jbmr.1997.12.5.769. [DOI] [PubMed] [Google Scholar]
  75. Zhu C., Bao G., Wang N. Cell mechanics: mechanical response, cell adhesion, and molecular deformation. Annu Rev Biomed Eng. 2000;2:189–226. doi: 10.1146/annurev.bioeng.2.1.189. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES