Skip to main content
Log in

Zonal Uniformity in Mechanical Properties of the Chondrocyte Pericellular Matrix: Micropipette Aspiration of Canine Chondrons Isolated by Cartilage Homogenization

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The pericellular matrix (PCM) is a region of tissue that surrounds chondrocytes in articular cartilage and together with the enclosed cells is termed the chondron. Previous studies suggest that the mechanical properties of the PCM, relative to those of the chondrocyte and the extracellular matrix (ECM), may significantly influence the stress–strain, physicochemical, and fluid-flow environments of the cell. The aim of this study was to measure the biomechanical properties of the PCM of mechanically isolated chondrons and to test the hypothesis that the Young's modulus of the PCM varies with zone of origin in articular cartilage (surface vs. middle/deep). Chondrons were extracted from articular cartilage of the canine knee using mechanical homogenization, and the elastic properties of the PCM were determined using micropipette aspiration in combination with theoretical models of the chondron as an elastic incompressible half-space, an elastic compressible bilayer, or an elastic compressible shell. The Young's modulus of the PCM was significantly higher than that reported for isolated chondrocytes but over an order of magnitude lower than that of the cartilage ECM. No significant differences were observed in the Young's modulus of the PCM between surface zone (24.0 ± 8.9 kPa) and middle/deep zone cartilage (23.2 ± 7.1 kPa). In combination with previous theoretical biomechanical models of the chondron, these findings suggest that the PCM significantly influences the mechanical environment of the chondrocyte in articular cartilage and therefore may play a role in modulating cellular responses to micromechanical factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alexopoulos, L. G., M. A. Haider, T. P. Vail, and F. Guilak. Alterations in the mechanical properties of the human chondrocyte pericellular matrix with osteoarthritis. J. Biomech. Eng. 125:323–333, 2003.

    Article  PubMed  Google Scholar 

  2. Alexopoulos, L. G., L. A. Setton, and F. Guilak. The biomechanical role of the chondrocyte pericellular matrix in articular cartilage. Acta Biomateriala 1:317–325, 2005.

    Article  Google Scholar 

  3. Alexopoulos, L. G., G. M. Williams, M. L. Upton, L. A. Setton, and F. Guilak. Osteoarthritic changes in the biphasic mechanical properties of the chondrocyte pericellular matrix in articular cartilage. J. Biomech. 38:509–517, 2005.

    Article  PubMed  Google Scholar 

  4. Aoki, T., T. Ohashi, T. Matsumoto, and M. Sato. The pipette aspiration applied to the local stiffness measurement of soft tissues. Ann. Biomed. Eng. 25:581–587, 1997.

    PubMed  Google Scholar 

  5. Aydelotte, M. B., and K. E. Kuettner. Differences between sub-populations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect. Tissue Res. 18:205–222, 1988.

    PubMed  Google Scholar 

  6. Baer, A. E., T. A. Laursen, F. Guilak, and L. A. Setton. The micromechanical environment of intervertebral disc cells determined by a finite deformation, anisotropic, and biphasic finite element model. J. Biomech. Eng. 125:1–11, 2003.

    Article  PubMed  Google Scholar 

  7. Baer, A. E., and L. A. Setton. The micromechanical environment of intervertebral disc cells: Effect of matrix anisotropy and cell geometry predicted by a linear model. J. Biomech. Eng. 122:245–251, 2000.

    Article  PubMed  Google Scholar 

  8. Benninghoff, A. Form und bau der Gelenkknorpel in ihren Beziehungen Zur Funktion. Zweiter Teil: der Aufbau des Gelenkknorpels in sienen Bezienhungen zur Funktion 2:783, 1925.

    Google Scholar 

  9. Buschmann, M. D., Y. A. Gluzband, A. J. Grodzinsky, and E. B. Hunziker. Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture. J. Cell Sci. 108:1497–1508, 1995.

    PubMed  Google Scholar 

  10. Chen, S. S., Y. H. Falcovitz, R. Schneiderman, A. Maroudas, and R. L. Sah. Depth-dependent compressive properties of normal aged human femoral head articular cartilage: Relationship to fixed charge density. Osteoarthritis Cartilage 9:561–569, 2001.

    Article  PubMed  Google Scholar 

  11. Eggli, P. S., W. Herrmann, E. B. Hunziker, and R. K. Schenk. Matrix compartments in the growth plate of the proximal tibia of rats. Anat. Rec. 211:246–257, 1985.

    Article  PubMed  Google Scholar 

  12. Greco, F., N. Specchia, F. Falciglia, A. Toesca, and S. Nori. Ultrastructural analysis of the adaptation of articular cartilage to mechanical stimulation. Ital. J. Orthop. Traumatol. 18:311–321, 1992.

    PubMed  Google Scholar 

  13. Guilak, F. Compression-induced changes in the shape and volume of the chondrocyte nucleus. J. Biomech. 28:1529–1542, 1995.

    Article  PubMed  Google Scholar 

  14. Guilak, F., G. R. Erickson, and H. P. Ting-Beall. The effects of osmotic stress on the viscoelastic and physical properties of articular chondrocytes. Biophys. J. 82:720–727, 2002.

    PubMed  Google Scholar 

  15. Guilak, F., W. R. Jones, H. P. Ting-Beall, and G. M. Lee. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage 7:59–70, 1999.

    Article  PubMed  Google Scholar 

  16. Guilak, F., B. C. Meyer, A. Ratcliffe, and V. C. Mow. The effects of matrix compression on proteoglycan metabolism in articular cartilage explants. Osteoarthritis Cartilage 2:91–101, 1994.

    Article  PubMed  Google Scholar 

  17. Guilak, F., and V. C. Mow. The mechanical environment of the chondrocyte: A biphasic finite element model of cell-matrix interactions in articular cartilage. J. Biomech. 33:1663–1673, 2000.

    Article  PubMed  Google Scholar 

  18. Guilak, F., A. Ratcliffe, and V. C. Mow. The mechanical environment of the chondrocyte: Effects of cell shape and intercellular spacing. In: Transactions of the Combined Meeting of the Orthopaedic Research Societies of USA, Japan, and Canada 1:171, 1991.

  19. Guilak, F., A. Ratcliffe, and V. C. Mow. Chondrocyte deformation and local tissue strain in articular cartilage: A confocal microscopy study. J. Orthop. Res. 13:410–421, 1995.

    Article  PubMed  Google Scholar 

  20. Guilak, F., R. L. Sah, and L. A. Setton. Physical regulation of cartilage metabolism. In: Basic Orthopaedic Biomechanics, edited by W. C. Hayes. Philadelphia: Lippincott-Raven, 1997, pp. 179–207.

  21. Haider, M. A. A radial biphasic model for local cell-matrix mechanics in articular cartilage. SIAM J. Appl. Math. 64:1588–1608, 2004.

    Article  Google Scholar 

  22. Haider, M. A., and F. Guilak. An axisymmetric boundary integral model for incompressible linear viscoelasticity: Application to the micropipette aspiration contact problem. J. Biomech. Eng. 122:236–244, 2000.

    Article  PubMed  Google Scholar 

  23. Haider, M. A., and F. Guilak. An axisymmetric boundary integral model for assessing elastic cell properties in the micropipette aspiration contact problem. J. Biomech. Eng. 124:586–595, 2002.

    Article  PubMed  Google Scholar 

  24. Helminen, H. J., J. Jurvelin, I. Kiviranta, K. Paukkonen, A. M. Saamanen, and M. Tammi. Joint loading effects on articular cartilage: A historical review. In: Joint Loading: Biology and Health of Articular Structures, edited by H. J. Helminen, I. Kiviranta, M. Tammi, A. M. Saamanen, K. Paukkonen, and J. Jurvelin. Bristol: Wright and Sons, 1987, pp. 1–46.

  25. Hing, W. A., A. F. Sherwin, and C. A. Poole. The influence of the pericellular microenvironment on the chondrocyte response to osmotic challenge. Osteoarthritis Cartilage 10:297–307, 2002.

    Article  PubMed  Google Scholar 

  26. Hochmuth, R. M. Micropipette aspiration of living cells. J. Biomech. 33:15–22, 2000.

    Article  PubMed  Google Scholar 

  27. Jones, W. R., H. P. Ting-Beall, G. M. Lee, S. S. Kelley, R. M. Hochmuth, and F. Guilak. Mechanical properties of human chondrocytes and chondrons from normal and osteoarthritic cartilage. Trans. Orthop. Res. Soc. 21:199, 1997.

    Google Scholar 

  28. Jones, W. R., H. P. Ting-Beall, G. M. Lee, S. S. Kelley, R. M. Hochmuth, and F. Guilak. Alterations in the Young's modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage. J. Biomech. 32:119–127, 1999.

    Article  PubMed  Google Scholar 

  29. Kim, Y. J., L. J. Bonassar, and A. J. Grodzinsky. The role of cartilage streaming potential, fluid flow and pressure in the stimulation of chondrocyte biosynthesis during dynamic compression. J. Biomech. 28:1055–1066, 1995.

    Article  PubMed  Google Scholar 

  30. Knight, M. M., D. A. Lee, and D. L. Bader. The influence of elaborated pericellular matrix on the deformation of isolated articular chondrocytes cultured in agarose. Biochim. Biophys. Acta 1405:67–77, 1998.

    Article  PubMed  Google Scholar 

  31. Knight, M. M., J. M. Ross, A. F. Sherwin, D. A. Lee, D. L. Bader, and C. A. Poole. Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose. Biochim. Biophys. Acta 1526:141–146, 2001.

    PubMed  Google Scholar 

  32. Koay, E. J., A. C. Shieh, and K. A. Athanasiou. Creep indentation of single cells. J. Biomech. Eng. 125:334–341, 2003.

    Article  PubMed  Google Scholar 

  33. Krishnan, R., S. Park, F. Eckstein, and G. A. Ateshian. Inhomogeneous cartilage properties enhance superficial interstitial fluid support and frictional properties, but do not provide a homogeneous state of stress. J. Biomech. Eng. 125:569–577, 2003.

    Article  PubMed  Google Scholar 

  34. Lee, G. M., C. A. Poole, S. S. Kelley, J. Chang, and B. Caterson. Isolated chondrons: A viable alternative for studies of chondrocyte metabolism in vitro. Osteoarthritis Cartilage 5:261–274, 1997.

    Article  PubMed  Google Scholar 

  35. Librizzi, N. N., W. R. Jones, D. S. Howell, L. A. Setton, and F. Guilak. Alterations in the viscoelastic properties of the pericellular matrix of articular cartilage in a canine model of joint disuse. Trans. Orthop. Res. Soc. 23:483, 1998.

    Google Scholar 

  36. Mow, V. C., C. C. Wang, and C. T. Hung. The extracellular matrix, interstitial fluid and ions as a mechanical signal transducer in articular cartilage. Osteoarthritis Cartilage 7:41–58, 1999.

    Article  PubMed  Google Scholar 

  37. Poole, C. A. Chondrons: The chondrocyte and its pericellular microenvironment. In: Articular Cartilage and Osteoarthritis, edited by V. C. Hascall. New York, London: Academic Press, 1992, pp. 201–220.

    Google Scholar 

  38. Poole, C. A. Articular cartilage chondrons: Form, function and failure. J. Anat. 191(Pt. 1):1–13, 1997.

    Article  PubMed  Google Scholar 

  39. Poole, C. A., S. Ayad, and J. R. Schofield. Chondrons from articular cartilage: I. Immunolocalization of type VI collagen in the pericellular capsule of isolated canine tibial chondrons. J. Cell Sci. 90(Pt. 4):635–643, 1988.

    PubMed  Google Scholar 

  40. Poole, C. A., M. H. Flint, and B. W. Beaumont. Chondrons in cartilage: Ultrastructural analysis of the pericellular microenvironment in adult human articular cartilages. J. Orthop. Res. 5:509–522, 1987.

    Article  PubMed  Google Scholar 

  41. Poole, C. A., T. Honda, S. J. Skinner, J. R. Schofield, K. F. Hyde, and H. Shinkai. Chondrons from articular cartilage (II): Analysis of the glycosaminoglycans in the cellular microenvironment of isolated canine chondrons. Connect. Tissue Res. 24:319–330, 1990.

    PubMed  Google Scholar 

  42. Sah, R. L., Y. J. Kim, J. Y. Doong, A. J. Grodzinsky, A. H. Plaas, and J. D. Sandy. Biosynthetic response of cartilage explants to dynamic compression. J. Orthop. Res. 7:619–636, 1989.

    Article  PubMed  Google Scholar 

  43. Schinagl, R. M., D. Gurskis, A. C. Chen, and R. L. Sah. Depth-dependent confined compression modulus of full-thickness bovine articular cartilage. J. Orthop. Res. 15:499–506, 1997.

    Article  PubMed  Google Scholar 

  44. Smirzai, J. A. The concept of the chondron as a biomechanical unit. In: Biopolymer und Biomechanik von Bindegewebssystemen, edited by F. Hartmann. Berlin: Academic Press, 1974, p. 87.

    Google Scholar 

  45. Stockwell, R. A. Biology of Cartilage Cells. Cambridge: Cambridge University Press, 1979.

    Google Scholar 

  46. Theret, D. P., M. J. Levesque, M. Sato, R. M. Nerem, and L. T. Wheeler. The application of a homogeneous half-space model in the analysis of endothelial cell micropipette measurements. J. Biomech. Eng. 110:190–199, 1988.

    PubMed  Google Scholar 

  47. Trickey, W. R., F. T. P. Baaijens, T. A. Laursen, L. G. Alexopoulos, and F. Guilak. Determination of the Poisson's ratio of the cell: Recovery properties of chondrocytes after release from complete micropipette aspiration. J. Biomech., in press (doi: 10.1016/j.jbiomech.2004.11.006).

  48. Trickey, W. R., G. M. Lee, and F. Guilak. Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. J. Orthop. Res. 18:891–898, 2000.

    Article  PubMed  Google Scholar 

  49. Valhmu, W. B., E. J. Stazzone, N. M. Bachrach, F. Saed-Nejad, S. G. Fischer, V. C. Mow, and A. Ratcliffe. Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch. Biochem. Biophys. 353:29–36, 1998.

    Article  PubMed  Google Scholar 

  50. Wang, C. C., X. E. Guo, D. Sun, V. C. Mow, G. A. Ateshian, and C. T. Hung. The functional environment of chondrocytes within cartilage subjected to compressive loading: A theoretical and experimental approach. Biorheology 39:11–25, 2002.

    PubMed  Google Scholar 

  51. Wang, C. C.-B., C. T. Hung, and V. C. Mow. Analysis of the effects of depth-dependent aggregate modulus on articular cartilage stress-relaxation behavior in compression. J. Biomech. 34(1):75–84, 2001.

    Article  PubMed  Google Scholar 

  52. Wong, M., P. Wuethrich, M. D. Buschmann, P. Eggli, and E. Hunziker. Chondrocyte biosynthesis correlates with local tissue strain in statically compressed adult articular cartilage. J. Orthop. Res. 15:189–196, 1997.

    Article  PubMed  Google Scholar 

  53. Wu, J. Z., W. Herzog, and M. Epstein. Modelling of location- and time-dependent deformation of chondrocytes during cartilage loading. J. Biomech. 32:563–572, 1999.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Farshid Guilak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guilak, F., Alexopoulos, L.G., Haider, M.A. et al. Zonal Uniformity in Mechanical Properties of the Chondrocyte Pericellular Matrix: Micropipette Aspiration of Canine Chondrons Isolated by Cartilage Homogenization. Ann Biomed Eng 33, 1312–1318 (2005). https://doi.org/10.1007/s10439-005-4479-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-005-4479-7

Keywords

Navigation