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.
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Almqvist, N., L. Backman, and S. Fredriksson. Imaging human erythrocyte spectrin with atomic force microscopy. Micron 25:227–232, 1994.
Bennett, V., and A. J. Baines. Spectrin and ankyrin-based pathways: Metazoan inventions for integrating cells into tissues. Physiol. Rev. 81:1353–1392, 2001.
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.
Bremer, A., and U. Aebi. The structure of the F-actin filament and the actin molecule. Curr. Opin. Cell Biol. 4:20–26, 1992.
Bustamante, C., J. F. Marko, E. D. Siggia, and S. Smith. Entropic elasticity of lambda-phage DNA. Science 265:1599–600, 1994.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Evans, E. A., R. Waugh, and L. Melnik. Elastic area compressibility modulus of red cell membrane. Biophys. J. 16:585–595, 1976.
Fowler, V. M. Regulation of actin filament length in erythrocytes and striated muscle. Curr. Opin. Cell Biol. 8:86–96, 1996.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Picart, C., P. Dalhaimer, and D. E. Discher. Actin protofilament orientation in deformation of the erythrocyte membrane skeleton. Biophys. J. 79:2987–3000, 2000.
Picart, C., and D. E. Discher. Actin protofilament orientation at the erythrocyte membrane. Biophys. J. 77:865–878, 1999.
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.
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.
Riley, W. F., and L. D. Sturges. Engineering Mechanics: Dynamics. New York: Wiley, 1995.
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.
Shoemake, K. Animating rotation with quaternion curves. Comp Graph (Proc. SIGGRAPH) 19:245–254, 1985.
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.
Speicher, D. W., and V. T. Marchesi. Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature 311:177–180, 1984.
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.
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.
Tozeren, A., R. Skalak, K. L. Sung, and S. Chien. Viscoelastic behavior of erythrocyte membrane. Biophys. J. 39:23–32, 1982.
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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
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DOI: https://doi.org/10.1007/s10439-005-4698-y