Advertisement

Modeling sickle hemoglobin fibers as one chain of coarse-grained particles

  • He Li
  • Ha Vi
  • George LykotrafitisEmail author
Conference paper
Part of the Conference Proceedings of the Society for Experimental Mechanics Series book series (CPSEMS)

Abstract

Sickle cell disease is a genetic disorder most commonly found in people of African descent and it is caused by the presence of abnormal hemoglobin S (HbS) in the patient’s red blood cells (RBCs). In the deoxygenated state, the defective hemoglobin tetramers polymerize forming stiff fibers which distort the cell and change its biomechanical properties. Because the HbS fibers play a vital role in the formation of the sickle-shaped RBC, the material properties and biomechanical behaviors of polymerized HbS fibers is a subject of intense research interest. Here, we introduce a solvent-free coarse-grain molecular dynamics (CGMD) model to simulate a single hemoglobin fiber as a chain of coarse-grained particles. A finitely extensible nonlinear elastic (FENE) potential is applied between consecutive particles. Meanwhile, a FENE-type bending potential is employed to model the bending resistance of HbS fibers. The parameters of the potentials are identified via comparison between the simulation results and the experimentally measured values of bending rigidity of single HbS fibers. The Langevin thermostat is employed to control the system temperature. This model will greatly facilitate future studies on the HbS polymerization, fiber bundle and gel formation as well as the interaction of between the HbS fiber bundles and the RBC membrane. In addition, the model can be easily adapted to study other filamentous protein assembles.

Keywords

Elastic properties zippering mechanisms Van der Waals and depletion forces HbS fiber model Langevin thermostat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ferrone, F.A., Polymerization and sickle cell disease: A molecular view. Microcirculation, 2004. 11: p. 115–128.Google Scholar
  2. 2.
    Christoph, G.W., J. Hofrichter, and W.A. Eaton, Understanding the shape of sickled red cells. Biophys J, 2005. 88: p. 1371–6.CrossRefGoogle Scholar
  3. 3.
    Aprelev, A., et al., The Effects of Erythrocyte Membranes on the Nucleation of Sickle Hemoglobin. Biophysical Journal, 2005. 88: p. 2815–2822.CrossRefGoogle Scholar
  4. 4.
    Lewis, M.R., L.J. Gross, and R. Josephs, Cryoelectron Microscopy of Deoxy-Sickle Hemoglobin Fibers. Microscopy Research and Technique, 1994. 27: p. 459–467.CrossRefGoogle Scholar
  5. 5.
    Turner, M.S., et al., Anisotropy in Sickle Hemoglobin Fibers from Variations in Bending and Twist. Journal of Molecular Biology, 2006. 357: p. 1422–1427.CrossRefGoogle Scholar
  6. 6.
    Wang, J.C., et al., Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths. Journal of Molecular Biology, 2002. 315: p. 601–612.CrossRefGoogle Scholar
  7. 7.
    Jones, C.W., et al., Interactions between sickle hemoglobin fibers. Faraday Discussions, 2003. 123: p. 221–236.CrossRefGoogle Scholar
  8. 8.
    Prabhakaran, M. and E.J. Michael, Molecular dynamics of sickle and normal hemoglobins. Biopolymers, 1993. 33: p. 735–742.CrossRefGoogle Scholar
  9. 9.
    Roufberg, A. and F.A. Ferrone, A model for the sickle hemoglobin fiber using both mutation sites. Protein Science, 2000. 9: p. 1031–1034.CrossRefGoogle Scholar
  10. 10.
    Reif, F., ed. Fundamentals of Statistical and Thermal Physics. 1965, McGraw-Hill, New York, NY.Google Scholar
  11. 11.
    Noguchi, H. and G. Gompper, Meshless membrane model based on the moving least-squares method. Physical Review E, 2006. 73: p. 021903.CrossRefGoogle Scholar
  12. 12.
    Underhill, P.T. and P.S. Doyle, On the coarse-graining of polymers into bead-spring chains. Journal of Non-Newtonian Fluid Mechanics, 2004. 122: p. 3–31.zbMATHCrossRefGoogle Scholar
  13. 13.
    Allen, M. and D. Tildesley, Computer Simulations of Liquids. 1987, New York: Clarendon Press.Google Scholar
  14. 14.
    Groot, R.D. and P.B. Warren, Dissipative particle dynamics: Bridging the gap between atomistic and mesoscopic simulation. Journal of Chemical Physics, 1997. 107: p. 4423–4435.CrossRefGoogle Scholar
  15. 15.
    Boal, D., Mechanics of the cell. 2002, Cambridge, United Kingdom: Cambridge University Press.Google Scholar
  16. 16.
    Turner, M.S., et al., Fluctuations in self-assembled sickle hemoglobin fibers. Langmuir, 2002. 18: p. 7182–7187.CrossRefGoogle Scholar
  17. 17.
    Jones, C.W., et al., Measuring Forces between Protein Fibers by Microscopy. Biophysical Journal, 2005. 88: p. 2433–2441.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Mechanical EngineeringUniversity of ConnecticutStorrsUSA

Personalised recommendations