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Direct observation of catch bonds involving cell-adhesion molecules

Abstract

Bonds between adhesion molecules are often mechanically stressed. A striking example is the tensile force applied to selectin–ligand bonds, which mediate the tethering and rolling of flowing leukocytes on vascular surfaces1,2,3. It has been suggested that force could either shorten bond lifetimes, because work done by the force could lower the energy barrier between the bound and free states4 (‘slip’), or prolong bond lifetimes by deforming the molecules such that they lock more tightly5,6 (‘catch’). Whereas slip bonds have been widely observed7,8,9,10,11,12,13,14, catch bonds have not been demonstrated experimentally. Here, using atomic force microscopy and flow-chamber experiments, we show that increasing force first prolonged and then shortened the lifetimes of P-selectin complexes with P-selectin glycoprotein ligand-1, revealing both catch and slip bond behaviour. Transitions between catch and slip bonds might explain why leukocyte rolling on selectins first increases and then decreases as wall shear stress increases9,15,16. This dual response to force provides a mechanism for regulating cell adhesion under conditions of variable mechanical stress.

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Figure 1: AFM system.
Figure 2: Binding specificity.
Figure 3: Lifetimes measured by AFM.
Figure 4: Lifetimes measured in a flow chamber.

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References

  1. Vestweber, D. & Blanks, J. E. Mechanisms that regulate the function of the selectins and their ligands. Physiol. Rev. 79, 181–213 (1999)

    Article  CAS  Google Scholar 

  2. McEver, R. P. & Cummings, R. D. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J. Clin. Invest. 100, 485–491 (1997)

    Article  CAS  Google Scholar 

  3. McEver, R. P. Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb. Haemost. 86, 746–756 (2001)

    Article  CAS  Google Scholar 

  4. Bell, G. I. Models for the specific adhesion of cells to cells. Science 200, 618–627 (1978)

    Article  ADS  CAS  Google Scholar 

  5. Dembo, M., Tourney, D. C., Saxman, K. & Hammer, D. The reaction-limited kinetics of membrane-to-surface adhesion and detachment. Proc. R. Soc. Lond. B 234, 55–83 (1988)

    Article  ADS  CAS  Google Scholar 

  6. Dembo, M. Lectures on Mathematics in the Life Sciences, Some Mathematical Problems in Biology 51–77 (American Mathematical Society, Providence, Rhode Island, 1994)

    Google Scholar 

  7. Alon, R., Hammer, D. A. & Springer, T. A. Lifetime of the P-selectin–carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374, 539–542 (1995)

    Article  ADS  CAS  Google Scholar 

  8. Pierres, A., Benoliel, A. M., Bongrand, P. & van der Merwe, P. A. Determination of the lifetime and force dependence of interactions of single bonds between surface-attached CD2 and CD48 adhesion molecules. Proc. Natl Acad. Sci. USA 93, 15114–15118 (1996)

    Article  ADS  CAS  Google Scholar 

  9. Alon, R., Chen, S., Puri, K. D., Finger, E. B. & Springer, T. A. The kinetics of L-selectin tethers and the mechanics of selectin-mediated rolling. J. Cell Biol. 138, 1169–1180 (1997)

    Article  CAS  Google Scholar 

  10. Chen, S. & Springer, T. A. An automatic braking system that stabilizes leukocyte rolling by an increase in selectin bond number with shear. J. Cell Biol. 144, 185–200 (1999)

    Article  CAS  Google Scholar 

  11. Smith, M. J., Berg, E. L. & Lawrence, M. B. A direct comparison of selectin-mediated transient, adhesive events using high temporal resolution. Biophys. J. 77, 3371–3383 (1999)

    Article  CAS  Google Scholar 

  12. Ramachandran, V. et al. Dimerization of a selectin and its ligand stabilizes cell rolling and enhances tether strength in shear flow. Proc. Natl Acad. Sci. USA 98, 10166–10171 (2001)

    Article  ADS  CAS  Google Scholar 

  13. Chen, S. & Springer, T. A. Selectin receptor–ligand bonds: Formation limited by shear rate and dissociation governed by the Bell model. Proc. Natl Acad. Sci. USA 98, 950–955 (2001)

    Article  ADS  CAS  Google Scholar 

  14. Merkel, R., Nassoy, P., Leung, A., Ritchie, K. & Evans, E. Energy landscapes of receptor–ligand bonds explored with dynamic force spectroscopy. Nature 397, 50–53 (1999)

    Article  ADS  CAS  Google Scholar 

  15. Finger, E. B. et al. Adhesion through L-selectin requires a threshold hydrodynamic shear. Nature 379, 266–269 (1996)

    Article  ADS  CAS  Google Scholar 

  16. Lawrence, M. B., Kansas, G. S., Kunkel, E. J. & Ley, K. Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E). J. Cell Biol. 136, 717–727 (1997)

    Article  CAS  Google Scholar 

  17. Geng, J.-G. et al. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature 343, 757–760 (1990)

    Article  ADS  CAS  Google Scholar 

  18. Moore, K. L. et al. The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine. J. Biol. Chem. 269, 23318–23327 (1994)

    CAS  PubMed  Google Scholar 

  19. Yago, T. et al. Distinct molecular and cellular contributions to stabilizing selectin-mediated rolling under flow. J. Cell Biol. 158, 787–799 (2002)

    Article  CAS  Google Scholar 

  20. Moore, K. L. et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J. Cell Biol. 128, 661–671 (1995)

    Article  CAS  Google Scholar 

  21. Moore, K. L., Varki, A. & McEver, R. P. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. J. Cell Biol. 112, 491–499 (1991)

    Article  CAS  Google Scholar 

  22. Chen, S., Alon, R., Fuhlbrigge, R. C. & Springer, T. A. Rolling and transient tethering of leukocytes on antibodies reveal specializations of selectins. Proc. Natl Acad. Sci. USA 94, 3172–3177 (1997)

    Article  ADS  CAS  Google Scholar 

  23. Ushiyama, S., Laue, T. M., Moore, K. L., Erickson, H. P. & McEver, R. P. Structural and functional characterization of monomeric soluble P-selectin and comparison with membrane P-selectin. J. Biol. Chem. 268, 15229–15237 (1993)

    CAS  PubMed  Google Scholar 

  24. Fritz, J., Katopodis, A. G., Kolbinger, F. & Anselmetti, D. Force-mediated kinetics of single P-selectin/ligand complexes observed by atomic force microscopy. Proc. Natl Acad. Sci. USA 95, 12283–12288 (1998)

    Article  ADS  CAS  Google Scholar 

  25. Leppänen, A., White, S. P., Helin, J., McEver, R. P. & Cummings, R. D. Binding of glycosulfopeptides to P-selectin requires stereospecific contributions of individual tyrosine sulfate and sugar residues. J. Biol. Chem. 275, 39569–39578 (2000)

    Article  Google Scholar 

  26. Somers, W. S., Tang, J., Shaw, G. D. & Camphausen, R. T. Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1. Cell 103, 467–479 (2000)

    Article  CAS  Google Scholar 

  27. Isberg, R. R. & Barnes, P. Dancing with the host; flow-dependent bacterial adhesion. Cell 110, 1–4 (2002)

    Article  CAS  Google Scholar 

  28. Hutter, J. L. & Bechhoefer, J. Calibration of atomic-force microscope tips. Rev. Sci. Instrum. 64, 1868–1873 (1993)

    Article  ADS  CAS  Google Scholar 

  29. McConnell, H. M., Watts, T. H., Weis, R. M. & Brian, A. A. Supported planar membranes in studies of cell–cell recognition in the immune system. Biochim. Biophys. Acta 864, 95–106 (1986)

    Article  CAS  Google Scholar 

  30. Wong, J. Y. et al. Polymer-cushioned bilayers. I. A structural study of various preparation methods using neutron reflectometry. Biophys. J. 77, 1445–1457 (1999)

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank V. Moy for providing the AFM design and training. This work was supported by grants from the National Institutes of Health.

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Correspondence to Cheng Zhu.

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Marshall, B., Long, M., Piper, J. et al. Direct observation of catch bonds involving cell-adhesion molecules. Nature 423, 190–193 (2003). https://doi.org/10.1038/nature01605

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