Skip to main content

Advertisement

Log in

Quantitative Analysis of Adhesion-Mediated Cell Migration in Three-Dimensional Gels of RGD-Grafted Collagen

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

Abstract

Adhesion-mediated migration is required in a number of physiological and pathological processes. A further quantitative understanding of the relationship between cell migration and cell-substratum adhesiveness may aid in therapeutic or tissue engineering applications. The aim of this work was to quantify three-dimensional cell migration as a function of increasing cell-substratum adhesiveness within reconstituted collagen gels. Cell-substratum adhesiveness was controlled by grafting additional adhesive peptides containing the well-characterized arginine-glycine-aspartic acid sequence to collagen. The three-dimensional migration of multiple individual cells was tracked in real time in an automated fashion for extended periods. Cell displacements were statistically analyzed and fit to a correlated persistent random walk model to estimate root-mean-square speed, directional persistence time, and random motility coefficient. Based on model parameter estimates, cell speed was found to be a monotonically decreasing function of increasing substratum adhesiveness, while the directional persistence time and random motility coefficient exhibited a biphasic dependence, with maximum values at approximately intermediate concentrations of grafted adhesive peptide and hence intermediate cell-substratum adhesiveness. In conclusion, these studies suggest an optimal adhesiveness for three-dimensional random migration, consistent with previous studies on two-dimensional surfaces. However, the maximum in random motility corresponded to a maximum in directional persistence, not in cell speed. © 2000 Biomedical Engineering Society.

PAC00: 8780Rb, 8714Ee, 8717Jj, 8715La, 8270Gg

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

  • 1Akiyama, S. K.Integrins in cell adhesion and signaling. Hum Cell.9:181-6, 1996.

    Google Scholar 

  • 2Albelda, S. M., S. A. Mette, D. E. Elder, R. Stewart, L. Damjanovich, M. Herlyn, and C. A. Buck. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res.50:6757-64, 1990.

    PubMed  Google Scholar 

  • 3Alt, W. Correlation Analysis of Two-Dimensional Locomotion Paths, Biological Motion, edited by W. Alt and G. Hoffmann. Berlin: Springer, 1990, pp.254-268.

    Google Scholar 

  • 4Aznavoorian, S., M. L. Stracke, J. Parsons, J. McClanahan, and L. A. Liotta. Integrin alphavbeta3 mediates chemotactic and haptotactic motiliby in human melanoma cells through different signaling pathways. J. Biol. Chem.271:3247-54, 1996.

    Google Scholar 

  • 5Bergman, A., and K. Zygourakis. Lymphocyte Motility and Adhesion on Fibronectin Surfaces Through the Beta-1 Integrin. 1998 AICHE Annual Meeting. Paper 278a, 1998 (unpublished).

  • 6Berman, A., G. Morozevich, I. Karmansky, A. Gleiberman, and V. Bychkova. Adhesion of mouse heptocytes to type I collagen: role of supramolecular forms and effect of proteolytic degradation. Biochem. Biophys. Res. Commun.194:351-7, 1993.

    Google Scholar 

  • 7Dedhar, S., E. Ruoslahti, and M. D. Pierschbacher. A cell surface receptor complex for collagen type I recognizes the Arg-Gly-Asp sequence. J. Cell Biol.104:585-93, 1987.

    Google Scholar 

  • 8Deryugina, E. I., M. A. Bourdon, R. A. Reisfeld, and A. Strongin. Remodeling of collagen matrix by human tumor cells requires activation and cell surface association of matrix metalloproteinase-2. Cancer Res.58:3743-50, 1998.

    Google Scholar 

  • 9Dickinson, R. B., S. Guido, and R. T. Tranquillo. Biased cell migration of fibroblasts exhibiting contact guidance in oriented collagen gels. Ann. Biomed. Eng.22:342-56, 1994.

    Google Scholar 

  • 10Dickinson, R. B., and R. T. Tranquillo. Optimal estimation of cell movement indices from the statistical analysis of cell tracking data. AIChE. J.39:1995-2010, 1993.

    Google Scholar 

  • 11DiMilla, P. A., J. A. Stone, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger. Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J. Cell Biol.122:729-37, 1993.

    Google Scholar 

  • 12Duband, J. L., S. Dufour, S. S. Yamada, K. M. Yamada, and J. P. Thiery. Neural crest cell locomotion induced by antibodies to beta 1 integrins. A tool for studying the roles of substratum molecular avidity and density in migration. J. Cell. Sci.98:517-32, 1991.

    Google Scholar 

  • 13Dunn, G. A.Characterizing a kinesis response: time averaged measures of cell speed and directional persistence. Agents Actions Suppl.12:14-33, 1983.

    Google Scholar 

  • 14Friedl, P., E. B. Brocker, and K. S. Zanker. Integrins, cell matrix interactions, and cell migration strategies: fundamental differences in leukocytes and tumor cells. Cell Adhes Commun.6:225-36, 1998.

    Google Scholar 

  • 15Friedl, P., F. Entschladen, C. Conrad, B. Niggemann, and K. S. Zanker. CD4+T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomoation. Eur. J. Immunol.28:2331-43, 1998.

    Google Scholar 

  • 16Friedl, P., K. Maaser, C. E. Klein, B. Niggemann, G. Krohne, and K. S. Zanker. Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of alpha2 and beta1 integrins and CD44. Cancer Res.57:2061-70, 1997.

    Google Scholar 

  • 17Friedl, P., K. S. Zanker, and E. B. Brocker. Cell migration strategies in 3-D extracellular matrix: differences in morphology, cell matrix interactions, and integrin function [In Process Citation]. Microsc. Res. Tech.43:369-78, 1998.

    Google Scholar 

  • 18Grinnell, F.Migration of human neutrophils in hydrated collagen lattices. J. Cell. Sci.58:95-108, 1982.

    Google Scholar 

  • 19Gunzer, M., E. Kampgen, E. B. Brocker, K. S. Zanker, and P. Friedl. Migration of dendritic cells in 3D-collagen lattices. Visualisation of dynamic interactions with the substratum and the distribution of surface structures via a novel confocal reflection imaging technique. Adv. Exp. Med. Biol.417:97-103, 1997.

    Google Scholar 

  • 20Haas, T., S. J. Davis, and J. A. Madri. Three-dimensional type I collagen lattices induce coordinate expression of matrix metalloproteinases MT1-MMP and MMP-2 in microvascular endothelial cells. J. Biol. Chem.273:3604-10, 1998.

    Google Scholar 

  • 21Huttenlocher, A., M. H. Ginsberg, and A. F. Horwitz. Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity. J. Cell Biol.134:1551-62, 1996.

    Google Scholar 

  • 22Huttenlocher, A., R. R. Sandborg, and A. F. Horwitz. Adhesion in cell migration. Curr. Opin. Cell Biol.7:697-706, 1995.

    Google Scholar 

  • 23Keely, P. J., A. M. Fong, M. M. Zutter, and S. A. Santoro. Alteration of collagen-dependent adhesion, motility, and morphogenesis by the expression of antisense alpha 2 integrin mRNA in mammary cells. J. Cell. Sci.108:595-607, 1995.

    Google Scholar 

  • 24Kramer, R. H., M. Vu, Y. F. Cheng, and D. M. Ramos. Iintegrin expression in malignant melanoma. Cancer Metastasis Rev.10:49-59, 1991.

    Google Scholar 

  • 25Kramer, R. H., and N. Marks. Identification of integrin collagen receptors on human melanoma cells. J. Biol. Chem.264:4684-8, 1989.

    Google Scholar 

  • 26Kuntz, R. M., and W. M. Saltzman. Neutrophil motility in extracellular matrix gels: mesh size and adhesion affect speed of migration. Biophys. J.72:1472-80, 1997.

    Google Scholar 

  • 27Lauffenburger, D. A., and A. F. Horwitz. Cell migration: a physically integrated molecular process. Cell84:359-69, 1996.

    Google Scholar 

  • 28Morla, A., Z. Zhang, and E. Ruoslahti. Superfibronectin is a functionally distinct form of fibronectin. Nature (London)367:193-6, 1994.

    Google Scholar 

  • 29Myles, J. L., B. T. Burgess, and R. B. Dickinson. Modification of the Adhesive Properties of Collagen by Covalent Grafting with RGD Peptides. (in press).

  • 30Palecek, S. P., A. Huttenlocher, A. F. Horwitz, and D. A. Lauffenburger. Physical and biochemical regulation of integrin release during rear detachment of migrating cells. J. Cell. Sci.111:929-40, 1998.

    Google Scholar 

  • 31Palecek, S. P., J. C. Loftus, M. H. Ginsberg, D. A. Lauffenburger, and A. F. Horwitz. Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness [published erratum appears in Nature 1997 Jul 10;388(6638):210]Nature (London)385:537-40, 1997.

    Google Scholar 

  • 32Pierschbacher, M. D., E. G. Hayman, and E. Ruoslahti. The cell attachment determinant in fibronectin. J. Cell. Biochem.28:115-26, 1985.

    Google Scholar 

  • 33Pierschbacher, M. D., and E. Ruoslahti. Variants of the cell recognition site of fibronectin that retain attachment-promoting activity. Proc. Natl. Acad. Sci. USA81:5985-8, 1984.

    Google Scholar 

  • 34Ruoslahti, E.RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol.12:697-715, 1996.

    PubMed  Google Scholar 

  • 35Ruoslahti, E., S. Suzuki, E. G. Hayman, C. R. Ill, and M. D. Pierschbacher. Purification and characterization of vitronectin. Methods Enzymol.144:430-7, 1987.

    Google Scholar 

  • 36Sheetz, M. P.Cell migration by graded attachment to substrates and contraction. Semin. Cell Biol.5:149-55, 1994.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burgess, B.T., Myles, J.L. & Dickinson, R.B. Quantitative Analysis of Adhesion-Mediated Cell Migration in Three-Dimensional Gels of RGD-Grafted Collagen. Annals of Biomedical Engineering 28, 110–118 (2000). https://doi.org/10.1114/1.259

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.259

Navigation