Annals of Biomedical Engineering

, Volume 33, Issue 4, pp 483–493

A Model for CD2/CD58-Mediated Adhesion Strengthening

Article
  • 59 Downloads

Abstract

Stable cell adhesion is vital for structural integrity and functional efficacy. Yet how low affinity adhesion molecules such as CD2 and CD58 can produce stable cell adhesion is still not completely understood. In this paper, we present a theoretical model that simulates the accumulation of CD2 and CD58 in the contact area of a Jurkat T lymphoblast and a CD58-containing substrate. The cell is assumed to have a spherical shape initially and it is allowed to spread gradually on a circular substrate. Mobile CD2 and CD58 can diffuse freely on both the cell and substrate. Their binding in the contact area is controlled by first-order kinetics. The contact area grows linearly with the total number of CD2/CD58 bonds. Cellular deformation and cytoskeleton involvement were not considered. This time-dependent moving-boundary problem was solved with the Crank–Nicolson finite difference scheme and the variable space grid method. Our simulated results are in reasonable agreement with the experimental observations. The role of diffusion becomes more and more prominent during the contact area increase, which is not sensitive to the kinetic rate constants tested in this study. However, it is very sensitive to the dissociation equilibrium constant and the concentrations of CD2 and CD58.

Keywords

Kinetics Diffusion Lymphocyte Moving boundary Equilibrium constant Receptor–ligand bonds 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bell, G. I. Models for the specific adhesion of cells to cells. Science 200:618–627, 1978.PubMedGoogle Scholar
  2. 2.
    Bell, G. I., M. Dembo, and P. Bongrand. Cell adhesion: Competition between nonspecific repulsion and specific bonding. Biophys. J. 45:1051–1064, 1984.PubMedGoogle Scholar
  3. 3.
    Burroughs, N. J., and C. Wulfing. Differential segregation in a cell-cell contact interface: The dynamics of the immunological synapse. Biophys J. 83:1784–1796, 2002.PubMedGoogle Scholar
  4. 4.
    Chan, P.-Y., M. B. Lawrence, M. L. Dustin, L. M. Ferguson, and T. A. Springer. The influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2. J. Cell Biol. 115:245–255, 1991.CrossRefPubMedGoogle Scholar
  5. 5.
    Coombs, D., M. Dembo, C. Wofsy, and B. Goldstein. Equilibrium thermodynamics of cell-cell adhesion mediated by multiple ligand-receptor pairs. Biophys J. 86:1408–1423, 2004.PubMedGoogle Scholar
  6. 6.
    Coombs, D., A. M. Kalergis, S. G. Nathenson, C. Wofsy, and B. Goldstein. Activated TCRs remain marked for internalization after dissociation from pMHC. Nat. Immunol. 3:926–931, 2002.CrossRefPubMedGoogle Scholar
  7. 7.
    Crank, J. Free and Moving Boundary Problems. New York: Oxford University Press, 1984.Google Scholar
  8. 8.
    Dustin, M. L. Adhesive bond dynamics in contacts between T lymphocytes and glass-supported planar bilayers reconstituted with the immunoglobulin-related adhesion molecule CD58. J. Biol. Chem. 272:15782–15788, 1997.CrossRefPubMedGoogle Scholar
  9. 9.
    Dustin, M. L. Making a little affinity go a long way: A topological view of LFA-1 regulation. Cell Adhesion Comm. 6:255–262, 1998.Google Scholar
  10. 10.
    Dustin, M. L., S. K. Bromley, M. M. Davis, and C. Zhu. Identification of self through two-dimensional chemistry and synapses. Annu. Rev. Cell Dev. Biol. 17:133–157, 2001.CrossRefPubMedGoogle Scholar
  11. 11.
    Dustin, M. L., and J. A. Cooper. The immunological synapse and the actin cytoskeleton: Molecular hardware for T cell signaling. Nat. Immunol. 1:23–29, 2000.CrossRefPubMedGoogle Scholar
  12. 12.
    Dustin, M. L., D. E. Golan, D.-M. Zhu, J. M. Miller, W. Meier, E. A. Davies, and P. A. van der Merwe. Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity. J. Biol. Chem. 272:30889–30898, 1997.PubMedGoogle Scholar
  13. 13.
    Dustin, M. L., M. W. Olszowy, A. D. Holdorf, J. Li, S. Bromley, N. Desai, P. Widder, F. Rosenberger, D. Van, P. M. Allen, and A. S. Shaw. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 94:667–677, 1998.PubMedGoogle Scholar
  14. 14.
    Dustin, M. L., L. M. Ferguson, P.-Y. Chan, T. A. Springer, and D. E. Golan. Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area. J. Cell Biol. 132:465–474, 1996.PubMedGoogle Scholar
  15. 15.
    Fletcher, C. A. J. Computational Techniques for Fluid Dynamics. Berlin, Germany: Springer-Verlag, 1991.Google Scholar
  16. 16.
    Grakoui, A., S. K. Bromley, C. Sumen, M. M. Davis, A. S. Shaw, P. M. Allen, and M. L. Dustin. The immunological synapse: A molecular machine controlling T cell activation. Science 285:221–227, 1999.PubMedGoogle Scholar
  17. 17.
    Lee, S. J., Y. Hori, J. T. Groves, M. L. Dustin, and A. K. Chakraborty. Correlation of a dynamic model for immunological synapse formation with effector functions: Two pathways to synapse formation. Trends Immunol. 23:492–499, 2002.PubMedGoogle Scholar
  18. 18.
    McCloskey, M. A., and M. M. Poo. Contact-induced redistribution of specific membrane components: Local accumulation and development of adhesion. J. Cell Biol. 102:2185–2196, 1986.PubMedGoogle Scholar
  19. 19.
    Mehta, P., R. D. Cummings, and R. P. McEver. Affinity and kinetic analysis of P-selectin binding to P-selectin glycoprotein ligand-1. J. Biol. Chem. 273:32506–32513, 1998.PubMedGoogle Scholar
  20. 20.
    Nicholson, M. W., A. N. Barclay, M. S. Singer, S. D. Rosen, and P. A. van der Merwe. Affinity and kinetic analysis of L-selectin (CD62L) binding to glycosylation-dependent cell-adhesion molecule-1. J. Biol. Chem. 273:763–770, 1998.PubMedGoogle Scholar
  21. 21.
    Pierres, A., A. M. Benoliel, P. Bongrand, and P. A. van der Merwe. Determination of the lifetime and force dependence of interactions of single bonds between surface-attached CD2 and CD48 adhesion and molecules. Proc. Natl. Acad. Sci. U.S.A. 93:15114–15118, 1996.PubMedGoogle Scholar
  22. 22.
    Qi, S. Y., J. T. Groves, and A. K. Chakraborty. Synaptic pattern formation during cellular recognition. Proc. Natl. Acad. Sci. U.S.A. 98:6548–6553, 2001.PubMedGoogle Scholar
  23. 23.
    Simon, S. I., J. D. Chambers, E. Butcher, and L. A. Sklar. Neutrophil aggregation is β2-integrin- and L-selectin-dependent in blood and isolated cells. J. Immunol. 149:2765–2771, 1992.PubMedGoogle Scholar
  24. 24.
    Springer, T. A. Adhesion receptors of the immune system. Nature 346:425–434, 1990.PubMedGoogle Scholar
  25. 25.
    Springer, T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol. 57:827–872, 1995.PubMedGoogle Scholar
  26. 26.
    van der Merwe, P. A., A. N. Barclay, D. W. Mason, E. A. Davies, B. P. Morgan, M. Tone, A. K. Krishnam, C. Ianelli, and S. J. Davis. Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. Biochemistry 33:10149–10160, 1994.PubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2005

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringWashington UniversitySaint Louis
  2. 2.Department of PathologyNew York University School of MedicineNew York
  3. 3.Department of Biomedical EngineeringWashington University in St. LouisSt. Louis

Personalised recommendations