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Nucleation and growth of fibres and gel formation in sickle cell haemoglobin

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Abstract

DEOXYGENATED sickle haemoglobin polymerizes into long 210-Å diameter fibres that distort and decrease the deformability of red blood cells, and cause sickle cell disease. The fibres consist of seven intertwined double strands1–3. They can form birefringent nematic liquid crystals (tactoids)4 and spherulites5,6. Rheologiealiy, the system behaves as a gel7,8. The equilibria show a phase separation and a solubility9–14. The reaction kinetics show a delay time, are then roughly exponential and are highly dependent on concentration and temperature9,10,15–18, and accord with the double nucleation model5,19. But these conclusions are derived from macroscopic data, without direct observation of individual fibres. We have now used non-invasive video-enhanced differential interference contrast (DIC) and dark-field microscopy to observe nucleation, growth and interaction of sickle deoxyhaemoglobin fibres in real time. The fibres originate both from centres that produce many radially distributed fibres and on the surface of pre-existing fibres, from which they then branch. The resulting network is cross-linked and dynamic in that it is flexible and continues to grow and cross-link. Our results support most aspects of the double nucleation model.

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References

  1. Wishner, B. C., Ward, K. B., Lattman, E. E. & Love, W. E. J. molec. Biol. 98, 179–194 (1975).

    Article  CAS  Google Scholar 

  2. Dykes, G. W., Crepeau, R. H. & Edelstein, S. J. Nature 272, 506–510 (1978).

    Article  ADS  CAS  Google Scholar 

  3. Dykes, G. W., Crepeau, R. H. & Edelstein, S. J. J. molec. Biol. 130, 451–472 (1979).

    Article  CAS  Google Scholar 

  4. Harris, J. W. Proc. Soc. exp. Biol. Med. 75, 197–201 (1950).

    Article  CAS  Google Scholar 

  5. Ferrone, F. A., Hofrichter, J., Sunshine, H. R. & Eaton, W. A. Biophys. J. 32, 361–380 (1980).

    Article  ADS  CAS  Google Scholar 

  6. Hofrichter, J. J. molec. Biol. 189, 553–571 (1986).

    Article  CAS  Google Scholar 

  7. Briehl, R. W. Nature 288, 622–624 (1980).

    Article  ADS  CAS  Google Scholar 

  8. Gabriel, D. A., Smith, L. A. & Johnson, C. S. Jr Arch. Biochem. Biophys. 211, 774–776 (1981).

    Article  CAS  Google Scholar 

  9. Hofrichter, J., Ross, P. D. & Eaton, W. A. in Proceedings of the Symposium on Molecular and Cellular Aspects of Sickle Cell Disease (eds Hercules, J. I., Cottam, G. L., Waterman, M. R. & Schechter, A. N.) 185–223 (US Dept. Health, Education and Welfare, Bethesda, Maryland, 1976).

    Google Scholar 

  10. Hofrichter, J., Ross, P. D. & Eaton, W. A. Proc. natn. Acad. Sci. U.S.A. 73, 3035–3039 (1976).

    Article  ADS  CAS  Google Scholar 

  11. Briehl, R. W. in Proceedings of the Symposium on Molecular and Cellular Aspects of Sickle Cell Disease (eds Hercules, J. I., Cottam, G. L., Waterman, M. R. & Schechter, A. N.) 145–181 (US Dept. Health, Education and Welfare, Bethesda, Maryland, 1976).

    Google Scholar 

  12. Briehl, R. W. J. molec. Biol. 123, 521–538 (1978).

    Article  CAS  Google Scholar 

  13. Magdoff-Fairchild, B., Poillon, W. N., Li, T.-L. & Bertles, J. F. Proc. natn. Acad. Sci. U.S.A. 73, 990–994 (1976).

    Article  ADS  CAS  Google Scholar 

  14. Goldberg, M. A., Husson, M. A. & Bunn, H. F. J. biol. Chem. 252, 3414–3421 (1977).

    CAS  PubMed  Google Scholar 

  15. Hofrichter, J., Ross, P. D. & Eaton, W. A. Proc. natn. Acad. Sci. U.S.A. 71, 4864–4868 (1974).

    Article  ADS  CAS  Google Scholar 

  16. Malfa, R. & Steinhardt, J. Biochem. biophys. Res. Commun. 59, 887–893 (1974).

    Article  CAS  Google Scholar 

  17. Ferrone, F. A., Hofrichter, J. & Eaton, W. A. J. molec. Biol. 183, 591–610 (1985).

    Article  CAS  Google Scholar 

  18. Briehl, R. W. Am. J. Pediat. Hemat. Oncol. 5, 390–398 (1983).

    Article  CAS  Google Scholar 

  19. Ferrone, F. A., Hofrichter, J. & Eaton, W. A. J. molec. Biol. 183, 611–631 (1985).

    Article  CAS  Google Scholar 

  20. Walker, R. A., Inoue, S. & Salmon, E. D. J. Cell Biol. 108, 931–937 (1989).

    Article  CAS  Google Scholar 

  21. Harris, J. W. & Bensusan, H. B. J. Lab. clin. Med. 86, 564–575 (1975).

    CAS  PubMed  Google Scholar 

  22. Briehl, R. W. Blood Cells 8, 201–212 (1982).

    CAS  PubMed  Google Scholar 

  23. Eaton, W. A., Hofrichter, J. & Ross, P. D. Blood 47, 621–627 (1976).

    CAS  PubMed  Google Scholar 

  24. Walker, R. A. et al. J. Cell Biol. 107, 1437–1448 (1988).

    Article  CAS  Google Scholar 

  25. Briehl, R. W. & Ewert, S. J. molec. Biol. 80, 445–458 (1973).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA

    Raymond E. Samuel & Robin W. Briehl

  2. Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, USA

    Robin W. Briehl

  3. Department of Biology, University of North Carolina, Chapel Hill, North Carolina, 27599, USA

    E. D. Salmon

Authors
  1. Raymond E. Samuel
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  2. E. D. Salmon
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  3. Robin W. Briehl
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Samuel, R., Salmon, E. & Briehl, R. Nucleation and growth of fibres and gel formation in sickle cell haemoglobin. Nature 345, 833–835 (1990). https://doi.org/10.1038/345833a0

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