Skip to main content
SpringerLink
Log in

3-D Nanomechanics of an Erythrocyte Junctional Complex in Equibiaxial and Anisotropic Deformations

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The erythrocyte membrane skeleton deforms constantly in circulation, but the mechanics of a junctional complex (JC) in the network is poorly understood. We previously proposed a 3-D mechanical model for a JC (Sung, L. A., and C. Vera. Protofilament and hexagon: A three-dimensional mechanical model for the junctional complex in the erythrocyte membrane skeleton. Ann Biomed Eng 31:1314–1326, 2003) and now developed a mathematical model to compute its equilibrium by dynamic relaxation. We simulated deformations of a single unit in the network to predict the tension of 6 αβ spectrin (Sp) (top, middle, and bottom pairs), and the attitude of the actin protofilament [pitch (θ), yaw (φ) and roll (ψ) angles]. In equibiaxial deformation, 6 Sp would not begin their first round of “single domain unfolding in cluster” until the extension ratio (λ) reach ~3.6, beyond the maximal sustainable λ of ~2.67. Before Sp unfolds, the protofilament would gradually raise its pointed end away from the membrane, while φ and ψ remain almost unchanged. In anisotropic deformation, protofilaments would remain tangent but swing and roll drastically at least once between λ i = 1.0 and ~2.8, in a deformation angle- and λ i -dependent fashion. This newly predicted nanomechanics in response to deformations may reveal functional roles previous unseen for a JC, and molecules associated with it, during erythrocyte circulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Almqvist, N., L. Backman, and S. Fredriksson. Imaging human erythrocyte spectrin with atomic force microscopy. Micron 25:227–232, 1994.

    Article  PubMed  Google Scholar 

  2. Bennett, V., and A. J. Baines. Spectrin and ankyrin-based pathways: Metazoan inventions for integrating cells into tissues. Physiol. Rev. 81:1353–1392, 2001.

    PubMed  Google Scholar 

  3. Bennett, V., and P. J. Stenbuck. The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes. Nature 280:468–473, 1979.

    Article  PubMed  Google Scholar 

  4. Bremer, A., and U. Aebi. The structure of the F-actin filament and the actin molecule. Curr. Opin. Cell Biol. 4:20–26, 1992.

    Article  PubMed  Google Scholar 

  5. Bustamante, C., J. F. Marko, E. D. Siggia, and S. Smith. Entropic elasticity of lambda-phage DNA. Science 265:1599–600, 1994.

    PubMed  Google Scholar 

  6. Byers, T. J., and D. Branton. Visualization of the protein associations in the erythrocyte membrane skeleton. Proc. Natl. Acad. Sci. USA 82:6153–6157, 1985.

    PubMed  Google Scholar 

  7. Carrion-Vazquez, M., A. F. Oberhauser, T. E. Fisher, P. E. Marszalek, H. Li, and J. M. Fernandez. Mechanical design of proteins studied by single-molecule force spectroscopy and protein engineering. Prog. Biophys. Mol. Biol. 74:63–91, 2000.

    Article  PubMed  Google Scholar 

  8. Chien, S., K.-L. P. Sung, R. Skalak, S. Usami, and A. Tozeren. Theoretical and experimental studies on viscoelastic properties of erythrocyte membrane. Biophys. J. 24:463–487, 1978.

    PubMed  Google Scholar 

  9. Chu, X., J. Chen, M. C. Reedy, C. Vera, K. L. Sung, and L. A. Sung. E-Tmod capping of actin filaments at the slow-growing end is required to establish mouse embryonic circulation. Am. J. Physiol. Heart. Circ. Physiol. 284:H1827–H1838, 2003.

    PubMed  Google Scholar 

  10. Discher, D. E., D. H. Boal, and S. K. Boey. Simulations of the erythrocyte cytoskeleton at large deformation. II. Micropipette aspiration. Biophys. J. 75:1584–1597, 1998.

    PubMed  Google Scholar 

  11. Discher, D. E., and P. Carl. New insights into red cell network structure, elasticity, and spectrin unfolding–a current review. Cell Mol. Biol. Lett. 6:593–606, 2001.

    PubMed  Google Scholar 

  12. Discher, D. E., N. Mohandas, and E. A. Evans. Molecular maps of red cell deformation: Hidden elasticity and in situ connectivity. Science 266:1032–1035, 1994.

    PubMed  Google Scholar 

  13. Evans, E. A. New membrane concept applied to the analysis of fluid shear- and micropipette-deformed red blood cells. Biophys. J. 13:941–954, 1973.

    PubMed  Google Scholar 

  14. Evans, E. A. Minimum energy analysis of membrane deformation applied to pipet aspiration and surface adhesion of red blood cells. Biophys. J. 30:265–284, 1980.

    PubMed  Google Scholar 

  15. Evans, E. A., R. Waugh, and L. Melnik. Elastic area compressibility modulus of red cell membrane. Biophys. J. 16:585–595, 1976.

    PubMed  Google Scholar 

  16. Fowler, V. M. Regulation of actin filament length in erythrocytes and striated muscle. Curr. Opin. Cell Biol. 8:86–96, 1996.

    Article  PubMed  Google Scholar 

  17. Hansen, J. C., R. Skalak, S. Chien, and A. Hoger. An elastic network model based on the structure of the red blood cell membrane skeleton. Biophys. J. 70:146–166, 1996.

    PubMed  Google Scholar 

  18. Hansen, J. C., R. Skalak, S. Chien, and A. Hoger. Influence of network topology on the elasticity of the red blood cell membrane skeleton. Biophys. J. 72:2369–2381, 1997.

    PubMed  Google Scholar 

  19. Harper, S. L., G. E. Begg, and D. W. Speicher. Role of terminal nonhomologous domains in initiation of human red cell spectrin dimerization. Biochemistry 40:9935–9943, 2001.

    Article  PubMed  Google Scholar 

  20. Kas, J., H. Strey, J. X. Tang, D. Finger, R. Ezzell, E. Sackmann, and P. A. Janmey. F-actin, a model polymer for semiflexible chains in dilute, semidilute, and liquid crystalline solutions. Biophys. J. 70:609–625, 1996.

    PubMed  Google Scholar 

  21. Knowles, D. W., L. Tilley, N. Mohandas, and J. A. Chasis. Erythrocyte membrane vesiculation: Model for the molecular mechanism of protein sorting. Proc. Natl. Acad. Sci. USA 94:12969–12974, 1997.

    Article  PubMed  Google Scholar 

  22. Law, R., S. Harper, D. W. Speicher, and D. E. Discher. Influence of lateral association on forced unfolding of antiparallel spectrin heterodimers. J. Biol. Chem. 279:16410–16416, 2004.

    Article  PubMed  Google Scholar 

  23. Lee, J. C., and D. E. Discher. Deformation-enhanced fluctuations in the red cell skeleton with theoretical relations to elasticity, connectivity, and spectrin unfolding. Biophys. J. 81:3178–3192, 2001.

    PubMed  Google Scholar 

  24. Lee, J. C., D. T. Wong, and D. E. Discher. Direct measures of large, anisotropic strains in deformation of the erythrocyte cytoskeleton. Biophys. J. 77:853–864, 1999.

    PubMed  Google Scholar 

  25. Liu, S. C., L. H. Derick, and J. Palek. Visualization of the hexagonal lattice in the erythrocyte membrane skeleton. J. Cell Biol. 104:527–536, 1987.

    Article  PubMed  Google Scholar 

  26. McGough, A. M., and R. Josephs. On the structure of erythrocyte spectrin in partially expanded membrane skeletons. Proc. Natl. Acad. Sci. USA 87:5208–5212, 1990.

    PubMed  Google Scholar 

  27. Onuma, E. K., P. S. Amenta, K. Ramaswamy, J. J. Lin, and K. M. Das. Autoimmunity in ulcerative colitis (UC): A predominant colonic mucosal B cell response against human tropomyosin isoform 5. Clin. Exp. Immunol. 121:466–471, 2000.

    Article  PubMed  Google Scholar 

  28. Picart, C., P. Dalhaimer, and D. E. Discher. Actin protofilament orientation in deformation of the erythrocyte membrane skeleton. Biophys. J. 79:2987–3000, 2000.

    PubMed  Google Scholar 

  29. Picart, C., and D. E. Discher. Actin protofilament orientation at the erythrocyte membrane. Biophys. J. 77:865–878, 1999.

    PubMed  Google Scholar 

  30. Reid, M. E., Y. Takakuwa, J. Conboy, G. Tchernia, and N. Mohandas. Glycophorin C content of human erythrocyte membrane is regulated by protein 4.1. Blood 75:2229–2234, 1990.

    PubMed  Google Scholar 

  31. Rief, M., J. Pascual, M. Saraste, and H. E. Gaub. Single molecule force spectroscopy of spectrin repeats: Low unfolding forces in helix bundles. J. Mol. Biol. 286:553–561, 1999.

    Article  PubMed  Google Scholar 

  32. Riley, W. F., and L. D. Sturges. Engineering Mechanics: Dynamics. New York: Wiley, 1995.

    Google Scholar 

  33. Shen, B. W., R. Josephs, and T. L. Steck. Ultrastructure of the intact skeleton of the human erythrocyte membrane. J. Cell Biol. 102:997–1006, 1986.

    Article  PubMed  Google Scholar 

  34. Shoemake, K. Animating rotation with quaternion curves. Comp Graph (Proc. SIGGRAPH) 19:245–254, 1985.

    Google Scholar 

  35. Smith, B. L., T.E. Schaffer, M. Viani, J.B. Thompson, N.A. Frederick, J. Kindt, A. Belcher, G.D. Stucky, D.E. Morse, and P.K. Hansma. Molecular mechanistic origin of the toughness of natural adhesives, fibers and composites. Nature 399:761–763, 1999.

    Article  Google Scholar 

  36. Speicher, D. W., and V. T. Marchesi. Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature 311:177–180, 1984.

    Article  PubMed  Google Scholar 

  37. Sung, K.-L. P., G. W. Schmid-Schönbein, R. Skalak, G. B. Schuessler, S. Usami, and S. Chien. Influence of physicochemical factors on rheology of human neutrophils. Biophys. J. 39:101–106, 1982.

    PubMed  Google Scholar 

  38. Sung, L. A., and C. Vera. Protofilament and hexagon: a three-dimensional mechanical model for the junctional complex in the erythrocyte membrane skeleton. Ann. Biomed. Eng. 31:1314–1326, 2003.

    Article  PubMed  Google Scholar 

  39. Tozeren, A., R. Skalak, K. L. Sung, and S. Chien. Viscoelastic behavior of erythrocyte membrane. Biophys. J. 39:23–32, 1982.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, 92093

    Carlos Vera & Lanping Amy Sung PhD

  2. Department of Mechanical and Aerospace Engineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, 92093

    Robert Skelton & Frederic Bossens

  3. Department of Bioengineering, and Center for Molecular Genetics, University of California, Mail Code 0412, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0412

    Lanping Amy Sung PhD

Authors
  1. Carlos Vera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Skelton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frederic Bossens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lanping Amy Sung PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lanping Amy Sung PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vera, C., Skelton, R., Bossens, F. et al. 3-D Nanomechanics of an Erythrocyte Junctional Complex in Equibiaxial and Anisotropic Deformations. Ann Biomed Eng 33, 1387–1404 (2005). https://doi.org/10.1007/s10439-005-4698-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-005-4698-y

Keywords

Search

Navigation