Annals of Biomedical Engineering

, Volume 22, Issue 4, pp 342–356

Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels

  • Richard B. Dickinson
  • Stefano Guido
  • Robert T. Tranquillo
Research Articles


We present here the first quantitative correlation for cell contact guidance in an oriented fibrillar network in terms of biased cell migration. The correlation is between the anisotropic cell diffusion parameter,DA=Dx/Dy, and the collagen gel birefringence, Δn, a measure of axially biased collagen fibril orientation in thex-direction. The cell diffusion coefficients,Dx andDy, measure the dispersal of cells in the directions coincident with and normal to the axis of fibril orientation, respectively. Three essential methodological components are involved: (i) exploiting the orienting effect of a magnetic field on collagen fibrils during fibrillogenesis to systematically prepare uniform axially oriented collagen gels; (ii) using a microscope/image analysis workstation with precise, computer-controlled rotating and translating stages to automate birefringence measurement and, along with rapid “coarse optical sectioning” via digital image processing, to enable 3-D cell tracking of many cells in multiple samples simultaneously; and (iii) employing a rigorous statistical analysis of the cell tracks to estimate the magnitude and precision of the direction-dependent cell diffusion coefficients,Dx andDy, that defineDA. We find that this measure of biased migration in contact guidance (DA) increases with increasing collagen fibril orientation (Δn) due mainly to a rapid enhancement of migration along the axis of fibril orientation at low levels of fibril orientation, and to a continued suppression of migration normal to the axis of fibril orientation at high levels of fibril orientation.


Contact guidance Collagen gel Migration Fibroblasts Image analysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barocas, V.H.; Tranquillo, R.T. Biphasic model andin vitro assays of cell-fibril mechanical interactions in tissueequivalent gels. In: V.C. Mow, ed. Cell mechanics and cellular engineering. Springer-Verlag: New York; 1994.Google Scholar
  2. 2.
    Dickinson, R.B.; McCarthy, J.B.; Tranquillo, R.T. Quantitative characterization of cell invasionin vitro: formulation and validation of a mathematical model of the collagen gel invasion assay. Ann. Biomed. Eng. 21:679–697; 1993.CrossRefPubMedGoogle Scholar
  3. 3.
    Dickinson, R.B.; Tranquillo, R.T. Optimal estimation of cell movement indices from the statistical analysis of cell tracking data. AIChE J 39:1995–2010; 1993.CrossRefGoogle Scholar
  4. 4.
    Dickinson, R.B.; Tranquillo, R.T. A stochastic model for adhesion-mediated cell random motility and haptotaxis. J. Math. Biol. 31:563–600; 1993.CrossRefPubMedGoogle Scholar
  5. 5.
    Dunn, G.A. Characterising a kinesis response: time averaged measures of cell speed and directional persistence. Agents Actions Suppl. 12:14–33; 1983.PubMedGoogle Scholar
  6. 6.
    Dunn, G.A. Chemotaxis as a form of directed cell behaviour: some theoretical considerations. In: Lackie, J.M.; Wilkinson, P.C., eds. Biology of the chemotactic response. Cambridge University Press: Cambridge; 1981: pp. 1–26.Google Scholar
  7. 7.
    Dunn, G.A. Contact guidance of cultured tissue cells: a survey of potentially relevant properties of the substratum. In: Bellairs, R.; Curtis, A.; Dunn, G., eds. Cell behaviour. Cambridge University Press: Cambridge; 1982: pp. 247–280.Google Scholar
  8. 8.
    Dunn, G.A.; Brown, A.F. A unified approach to analysing cell motility. J. Cell. Sci. Suppl. 8:81–102; 1987.PubMedGoogle Scholar
  9. 9.
    Freshney, R.I. Culture of animal cells: a manual of basic technique, 2nd ed. Alan R. Liss, Inc.: New York; 1987.Google Scholar
  10. 10.
    Furth, V.R. Die Brownshe Bewegung bei Berucksichtigung einer Persistenze der Bewegungsrichtung. Mit Anwendungen auf die Bewegung lebender Infusorien. Zeit. f. Phys. II:244–256; 1920.Google Scholar
  11. 11.
    Gail, M.H.; Boone, C.W. The locomotion of mouse fibroblasts in tissue culture. Biophys. J. 10:980–993; 1970.PubMedGoogle Scholar
  12. 12.
    Guido, S.; Tranquillo, R.T. A methodology for the systematic and quantitative study of cell contact guidance in oriented collagen gels: correlation of fibroblast orientation and gel birefringence. J. Cell. Sci. 105:317–331; 1993.PubMedGoogle Scholar
  13. 13.
    Harris, A.K. Tissue culture cells on deformable substrata: biomechanical implications. J. Biomech. Eng. 106:19–24; 1984.PubMedGoogle Scholar
  14. 14.
    Harris, A.K.; Stopak, D.; Wild, P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature 290:249–251; 1981.CrossRefPubMedGoogle Scholar
  15. 15.
    Haston, W.S.; Shields, J.M.; Wilkinson, P.C. The orientation of fibroblasts and neutrophils on elastic substrata. Exp. Cell. Res. 146:117–126; 1983.CrossRefPubMedGoogle Scholar
  16. 16.
    Heath, J.P.; Hedlund, K.-O. Locomotion and cell surface movements of fibroblasts in fibrillar collagen gels. Scan. Electron Microsc. 4:2031–2043; 1984.Google Scholar
  17. 17.
    Inoue, S. Video microscopy. Plenum Press: New York; 1987.Google Scholar
  18. 18.
    Matthes, T.; Gruler, H. Analysis of cell locomotion. Contact guidance of human polymorphonuclear leukocytes. Eur. Biophys. J. 15:343–357; 1988.CrossRefPubMedGoogle Scholar
  19. 19.
    Modis, L. Organization of the extracellular matrix: a polarization microscopic approach. CRC Press: Boca Raton; 1991.Google Scholar
  20. 20.
    Noble, P.B. Extracellular matrix and cell migration: locomotory characteristics of MOS-11 cells within a three-dimensional hydrated collagen lattice. J. Cell. Sci. 87:241–248; 1987.PubMedGoogle Scholar
  21. 21.
    Noble, P.B.; Boyarsky, A. Analysis of cell three-dimensional locomotory vectors. Exp. Cell. Biol. 56:289–296; 1988.PubMedGoogle Scholar
  22. 22.
    Noble, P.B.; Shields, E.D. Time-based changes in fibroblast three-dimensional locomotory characteristics and phenotypes. Exp. Cell. Biol. 57:238–245; 1989.PubMedGoogle Scholar
  23. 23.
    Othmer, H. G.; Dunbar, S. R.; Alt, W. Models of dispersal in biological systems. J. Math. Biol. 26:263–298; 1988.CrossRefPubMedGoogle Scholar
  24. 24.
    Parkhurst, M.R.; Saltzman, W.M. Quantification of human neurotrophil motility in three-dimensional collagen gels. Biophys. J. 61:306–315; 1992.PubMedGoogle Scholar
  25. 25.
    Stopak, D.; Harris, A.K. Connective tissue morphogenesis by fibroblast traction. I. Tissue culture observations. Dev. Biol. 90:383–398; 1982.CrossRefPubMedGoogle Scholar
  26. 26.
    Torbet, J.; Ronziere, M.C. Magnetic alignment of collagen during self-assembly. Biochem. J. 219:1057–1059; 1984.PubMedGoogle Scholar
  27. 27.
    Tranquillo, R.T.; Alt, W. Glossary of terms concerning oriented movement. In: Alt, W.; Hoffman, G., eds. Biological motion. Springer-Verlag: Berlin; 1990, Vol. 89: pp. 510–517.Google Scholar
  28. 28.
    Tranquillo, R.T.; Durrani, M.A.; Moon, A.G. Tissue engineering science: consequences of cell traction force. Cytotechnology 10:225–250; 1992.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 1994

Authors and Affiliations

  • Richard B. Dickinson
    • 3
  • Stefano Guido
    • 3
  • Robert T. Tranquillo
    • 3
  1. 1.Department of Chemical EngineeringUniversity of FloridaGainesville
  2. 2.Dipartimento di Ingegneria Chimica, P. le V. TecchioUniversita Degli Studi di Napoli Federico IINapoliItaly
  3. 3.Department of Chemical Engineering and Materials ScienceUniversity of MinnesotaMinneapolis

Personalised recommendations