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A Model for CD2/CD58-Mediated Adhesion Strengthening

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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.

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References

  1. Bell, G. I. Models for the specific adhesion of cells to cells. Science 200:618–627, 1978.

    CAS  PubMed  Google Scholar 

  2. Bell, G. I., M. Dembo, and P. Bongrand. Cell adhesion: Competition between nonspecific repulsion and specific bonding. Biophys. J. 45:1051–1064, 1984.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  7. Crank, J. Free and Moving Boundary Problems. New York: Oxford University Press, 1984.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  15. Fletcher, C. A. J. Computational Techniques for Fluid Dynamics. Berlin, Germany: Springer-Verlag, 1991.

    Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  24. Springer, T. A. Adhesion receptors of the immune system. Nature 346:425–434, 1990.

    CAS  PubMed  Google Scholar 

  25. Springer, T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol. 57:827–872, 1995.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Engineering, Washington University, Saint Louis, MO

    Jin-Yu Shao PhD & Yan Yu

  2. Department of Pathology, New York University School of Medicine, New York

    Michael L. Dustin

Authors
  1. Jin-Yu Shao PhD
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  2. Yan Yu
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  3. Michael L. Dustin
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Correspondence to Jin-Yu Shao PhD.

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Shao, JY., Yu, Y. & Dustin, M.L. A Model for CD2/CD58-Mediated Adhesion Strengthening. Ann Biomed Eng 33, 483–493 (2005). https://doi.org/10.1007/s10439-005-2504-5

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  • DOI: https://doi.org/10.1007/s10439-005-2504-5

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