Skip to main content

Abstract

The chapter addresses the question whether hemoglobin (protein) can “sense” body temperature. When human red blood cells (RBCs) were aspirated into 1.3μm pipettes (∆P = −2.3 kPa), a transition from blocking the pipette below T c = 36.3±0.3 °C to passing it above T c occurred (passage transition). With a 1.1 μm pipette no passage was seen and RBC volume measurements were possible. With increasing temperature RBCs lost volume significantly faster below than above T c =36.4±0.7 °C (RBC volume transition). Colloid osmotic pressure (COP) measurements of RBCs in plasma (25 °C ≤ T ≤ 39.5 °C) showed a turning point at T c = 37.1±0.2 °C above which the COP rapidly decreased (COP transition). In NMR T1 relaxation time measurements the T1 of RBCs in plasma changed from a linear (r = 0.99) increment of T1 below T c = 37±1 °C at a rate of 0.023 s/K, into a parallel to the temperature axis above this point (RBC T1 transition). In conclusion: during micropipette aspiration, an amorphous gel forms in the spherical trail of the aspirated RBC, consisting of mostly hemoglobin and water. At T c a fluidization of the gel occurs and non-covalent bonds (Van-der-Waals bonds) break down due to thermal energy enabling cell passage. The passage, the volume, the COP, and the RBC T1 transitions all happen at distinct T c close to body temperature. We suggest a transition gel to liquid to be a common mechanism of these phenomena. T c may mark the set point of a species’ normal body temperature which might be inscribed in the primary structure of a species’ hemoglobin and possibly in other proteins. The concepts of non-linearity and phase transitions in protein-water systems might bring novel exciting aspects into cell biology.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Artmann, G.M. 1995. Microscopic photometric quantification of stiffness and relaxation time of red blood cells in a flow chamber. Biorheology 32:553-570.

    Article  Google Scholar 

  2. Artmann, G.M., L. Burns, J.M. Canaves, A. Temiz-Artmann, G.W. Schmid-Schonbein, S. Chien, and C. Maggakis-Kelemen. 2004. Circular dichroism spectra of human hemoglobin reveal a reversible structural transition at body temperature. Eur. Biophys. J. 33:490-496.

    Article  Google Scholar 

  3. Artmann, G. M., I. Digel, K.F. Zerlin, Ch.Maggakis-Kelemen, Pt.Linder, D. Porst, P. Kayser, G. Dikta, and A. Temiz Artmann. 2007. Hemoglobin senses body temperature. 2007. Unpublished Work, submitted to Eur. Biophys. J.

    Google Scholar 

  4. Artmann, G.M., C. Kelemen, D. Porst, G. Buldt, and S. Chien. 1998. Temperature transitions of protein properties in human red blood cells. Biophys. J. 75:3179-3183.

    Article  Google Scholar 

  5. Artmann, G.M., A. Li, J. Ziemer, G. Schneider, and U. Sahm. 1996. A photometric method to analyze induced erythrocyte shape changes. Biorheology 33:251-265.

    Article  Google Scholar 

  6. Artmann, G.M., K.L. Sung, T. Horn, D. Whittemore, G. Norwich, and S. Chien. 1997. Micropipette aspiration of human erythrocytes induces echinocytes via membrane phospholipid translocation. Biophys. J. 72:1434-1441.

    Google Scholar 

  7. Bastianetto, S., M. Danik, F. Mennicken, S. Williams, and R. Quirion. 2006. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation. BMC. Neurosci. 7:28.

    Article  Google Scholar 

  8. Bessis, M. and L.S. Lessin. 1970. The discocyte-echinocyte equilibrium of the normal and pathologic red cell. Blood 36:399-403.

    Google Scholar 

  9. Blow, D. 2002. Max Perutz (1914-2002). Q. Rev. Biophys. 35:201-204.

    Google Scholar 

  10. Bohm, G., R. Muhr, and R. Jaenicke. 1992. Quantitative analysis of protein far UV circular dichroism spectra by neural networks. Protein Eng 5:191-195.

    Article  Google Scholar 

  11. Buldt, G., Artmann, G. M., Zaccai, G., Digel, I., and Stadler, A. M. Differences of water and D2O binding to proteins; temperature dependent DSC measurements and lattice constants of hemoglobin crystals. 7-5-2007. Personal Communication

    Google Scholar 

  12. Cameron, I.L., V.A. Ord, and G.D. Fullerton. 1988. Water of hydration in the intra- and extra-cellular environment of human erythrocytes. Biochem. Cell Biol. 66:1186-1199.

    Article  Google Scholar 

  13. Chen, J.Y., L.S. Brunauer, F.C. Chu, C.M. Helsel, M.M. Gedde, and W.H. Huestis. 2003. Selective amphipathic nature of chlorpromazine binding to plasma membrane bilayers. Biochim. Biophys. Acta 1616:95-105.

    Article  Google Scholar 

  14. Chien, S. 1981. Filterability and other methods of approaching red cell deformability. Determinants of blood viscosity and red cell deformability. Scand. J. Clin. Lab Invest Suppl 156:7-12.

    Article  Google Scholar 

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

    Google Scholar 

  16. Cioni, P. and G.B. Strambini. 2002. Effect of heavy water on protein flexibility and lattice constants of protein crystals. Biophys. J. 82:3246-3253.

    Article  Google Scholar 

  17. Claessens, M.M., F.A. Leermakers, F.A. Hoekstra, and M.A. Stuart. 2007. Opposing effects of cation binding and hydration on the bending rigidity of anionic lipid bilayers. J. Phys. Chem. B 111:7127-7132.

    Article  Google Scholar 

  18. Cribier, S., J. Sainte-Marie, and P.F. Devaux. 1993. Quantitative comparison between aminophospholipid translocase activity in human erythrocytes and in K562 cells. Biochim. Biophys. Acta 1148:85-90.

    Article  Google Scholar 

  19. Dadarlat, V.M. and C.B. Post. 2006. Decomposition of protein experimental compressibility into intrinsic and hydration shell contributions. Biophys. J. 91:4544-4554.

    Article  Google Scholar 

  20. Dencher, N.A., H.J. Sass, and G. Buldt. 2000. Water and bacteriorhodopsin: structure, dynamics, and function. Biochim. Biophys. Acta 1460:192-203.

    Article  Google Scholar 

  21. Deuticke, B. 1968. Transformation and restoration of biconcave shape of human erythrocytes induced by amphiphilic agents and changes of ionic environment. Biochim. Biophys. Acta 163:494-500.

    Article  Google Scholar 

  22. Devaux, P.F. 1992. Protein involvement in transmembrane lipid asymmetry. Annu. Rev. Biophys. Biomol. Struct. 21:417-439.

    Article  Google Scholar 

  23. Digel, I, Engels, S, Hoffmann, B, Porst, D., and Artmann, G. M. Differential Scanning Calorimetry and micropipette experiments of human Red Blood Cells. 7-8-0007. Unpublished Work

    Google Scholar 

  24. Digel, I., C. Maggakis-Kelemen, K.F. Zerlin, P. Linder, N. Kasischke, P. Kayser, D. Porst, A.A. Temiz, and G.M. Artmann. 2006. Body temperature-related structural transitions of monotremal and human hemoglobin. Biophys. J. 91:3014-3021.

    Article  Google Scholar 

  25. Dikta, G., M. Kvesic, and C. Schmidt. 2006. Bootstrap Approximations in Model Checks for Binary Data. Journal of the American Statistical Association 101:521-530.

    Article  MATH  MathSciNet  Google Scholar 

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

    Article  Google Scholar 

  27. Eisenberg, H. 2003. Adair was right in his time. Eur. Biophys. J. 32:406-411.

    Article  Google Scholar 

  28. Engstrom, K.G. and H.J. Meiselman. 1996. Effects of pressure on red blood cell geometry during micropipette aspiration. Cytometry 23:22-27.

    Article  Google Scholar 

  29. Engstrom, K.G. and H.J. Meiselman. 1997. Combined use of micropipette aspiration and perifusion for studying red blood cell volume regulation. Cytometry 27:345-352.

    Article  Google Scholar 

  30. Evans, E.A. 1983. Bending elastic modulus of red blood cell membrane derived from buckling instability in micropipet aspiration tests. Biophys. J. 43:27-30.

    Google Scholar 

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

    Article  Google Scholar 

  32. Fairbanks, G., T.L. Steck, and D.F. Wallach. 1971. Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane. Biochemistry 10:2606-2617.

    Article  Google Scholar 

  33. Farinas, J., A.N. Van Hoek, L.B. Shi, C. Erickson, and A.S. Verkman. 1993. Nonpolar environment of tryptophans in erythrocyte water channel CHIP28 determined by fluorescence quenching. Biochemistry 32:11857-11864.

    Article  Google Scholar 

  34. Fasman, G.D. 1996. Circular Dichroism and the Conformational Analysis of Biomolecules. Plenum Press, New York.

    Google Scholar 

  35. Finnie, M., G.D. Fullerton, and I.L. Cameron. 1986. Molecular masking and unmasking of the paramagnetic effect of iron on the proton spin-lattice (T1) relaxation time in blood and blood clots. Magn Reson. Imaging 4:305-310.

    Article  Google Scholar 

  36. Fischer, T.M. 1989. Erythrocyte deformation under shear flow. Blood 73:1074-1075.

    Google Scholar 

  37. Fischer, T.M. 2004. Shape memory of human red blood cells. Biophys. J. 86:3304-3313.

    Article  Google Scholar 

  38. Friederichs, E., R.A. Farley, and H.J. Meiselman. 1992. Influence of calcium permeabilization and membrane-attached hemoglobin on erythrocyte deformability. Am. J. Hematol. 41:170-177.

    Article  Google Scholar 

  39. Goldenfeld, N. 1992. Lectures on Phase Transitions and the Renormalization Group.

    Google Scholar 

  40. Grebe, R. and M.J. Zuckermann. 1990. Erythrocyte shape simulation by numerical optimization. Biorheology 27:735-746.

    Google Scholar 

  41. Heller, K.B. and M. Hofer. 1975. Temperature dependence of the energy-linked monosaccharide transport across the cell membrane of Rhodotorula gracilis. J. Membr. Biol. 21:261-271.

    Article  Google Scholar 

  42. Hochmuth, R.M. 1993. Measuring the mechanical properties of individual human blood cells. J. Biomech. Eng 115:515-519.

    Article  Google Scholar 

  43. Hochmuth, R.M. and R.E. Waugh. 1987. Erythrocyte membrane elasticity and viscosity. Annu. Rev. Physiol 49:209-219.

    Article  Google Scholar 

  44. Hochmuth, R.M., P.R. Worthy, and E.A. Evans. 1979. Red cell extensional recovery and the determination of membrane viscosity. Biophys. J. 26:101-114.

    Google Scholar 

  45. Hueck, I.S., H.G. Hollweg, G.W. Schmid-Schonbein, and G.M. Artmann. 2000. Chlorpromazine modulates the morphological macro- and microstructure of endothelial cells. Am. J. Physiol Cell Physiol 278:C873-C878.

    Google Scholar 

  46. Ikeda, M., A. Kihara, and Y. Igarashi. 2006. Lipid asymmetry of the eukaryotic plasma membrane: functions and related enzymes. Biol. Pharm. Bull. 29:1542-1546.

    Article  Google Scholar 

  47. Jay, D.G. 1996. Role of band 3 in homeostasis and cell shape. Cell 86:853-854.

    Article  Google Scholar 

  48. Kassab, G.S. 2004. Y.C. "Bert" Fung: the father of modern biomechanics. Mech. Chem. Biosyst. 1:5-22.

    Google Scholar 

  49. Kelemen, C., S. Chien, and G.M. Artmann. 2001. Temperature transition of human hemoglobin at body temperature: effects of calcium. Biophys. J. 80:2622-2630.

    Article  Google Scholar 

  50. Kharakoz, D.P. and A.P. Sarvazyan. 1993. Hydrational and intrinsic compressibilities of globular proteins. Biopolymers 33:11-26.

    Article  Google Scholar 

  51. Kinderlerer, J., H. Lehmann, and K.F. Tipton. 1970. Thermal denaturation of human haemoglobins. Biochem. J. 119:66-67.

    Google Scholar 

  52. Kinderlerer, J., H. Lehmann, and K.F. Tipton. 1973. The thermal denaturation of human oxyhaemoglobins A, A2, C and S. Biochem. J. 135:805-814.

    Google Scholar 

  53. Landau, L.D.a.L.E.M. 2007. Statistical Physics Part 1. Pergamon.

    Google Scholar 

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

    Google Scholar 

  55. Li, Z., S. Raychaudhuri, and A.J. Wand. 1996. Insights into the local residual entropy of proteins provided by NMR relaxation. Protein Sci. 5:2647-2650.

    Google Scholar 

  56. Lucas, C.E., A.M. Ledgerwood, W.J. Rachwal, D. Grabow, and J.M. Saxe. 1991. Colloid oncotic pressure and body water dynamics in septic and injured patients. J. Trauma 31:927-931.

    Google Scholar 

  57. Michnik, A., Z. Drzazga, A. Kluczewska, and K. Michalik. 2005. Differential scanning microcalorimetry study of the thermal denaturation of haemoglobin. Biophys. Chem. 118:93-101.

    Article  Google Scholar 

  58. Mohandas, N. and J.A. Chasis. 1993. Red blood cell deformability, membrane material properties and shape: regulation by transmembrane, skeletal and cytosolic proteins and lipids. Semin. Hematol. 30:171-192.

    Google Scholar 

  59. Mozo, J., Y. Emre, F. Bouillaud, D. Ricquier, and F. Criscuolo. 2005. Thermoregulation: what role for UCPs in mammals and birds? Biosci. Rep. 25:227-249.

    Article  Google Scholar 

  60. Muller, G.H., H. Schmid-Schonbein, and H.J. Meiselman. 1992. Development of viscoelasticity in heated hemoglobin solutions. Biorheology 29:203-216.

    Google Scholar 

  61. Niimura, N., T. Chatake, K. Kurihara, and M. Maeda. 2004. Hydrogen and hydration in proteins. Cell Biochem. Biophys. 40:351-369.

    Article  Google Scholar 

  62. Nomoto, S., M. Shibata, M. Iriki, and W. Riedel. 2004. Role of afferent pathways of heat and cold in body temperature regulation. Int. J. Biometeorol. 49:67-85.

    Article  Google Scholar 

  63. Oberwinkler, J. 2007. TRPM3, a biophysical enigma? Biochem. Soc. Trans. 35:89-90.

    Article  Google Scholar 

  64. Penzlin, H. 1977. Lehrbuch der Tierphysiologie. Gustav Fischer Verlag, Stuttgart New York.

    Google Scholar 

  65. Pierre, S.V. and Z. Xie. 2006. The Na,K-ATPase receptor complex: its organization and membership. Cell Biochem. Biophys. 46:303-316.

    Article  Google Scholar 

  66. Pollack, G.H. 2001a. Cells, Gels and the Engines of life. Ebner and Sons, Seattle.

    Google Scholar 

  67. Pollack, G.H. 2001b. Is the cell a gel–and why does it matter? Jpn. J. Physiol 51:649-660.

    Article  Google Scholar 

  68. Poschl, J.M., C. Leray, P. Ruef, J.P. Cazenave, and O. Linderkamp. 2003. Endotoxin binding to erythrocyte membrane and erythrocyte deformability in human sepsis and in vitro. Crit Care Med. 31:924-928.

    Article  Google Scholar 

  69. Roche, J., A. Roche, G.S. Adair, and M.E. Adair. 1932. The osmotic pressure of globin. Biochem. J. 26:1811-1828.

    Google Scholar 

  70. Ross, F.P. and A.M. Christiano. 2006. Nothing but skin and bone. J. Clin. Invest 116:1140-1149.

    Article  Google Scholar 

  71. Sahu, S.K., S.N. Gummadi, N. Manoj, and G.K. Aradhyam. 2007. Phospholipid scramblases: an overview. Arch. Biochem. Biophys. 462:103-114.

    Article  Google Scholar 

  72. Schmid-Schonbein, H., H. Heidtmann, and R. Grebe. 1986a. Spectrin, red cell shape and deformability. I. Membrane curvature in genetic spectrin deficiency. Blut 52:131-147.

    Article  Google Scholar 

  73. Schmid-Schonbein, H., H. Heidtmann, and R. Grebe. 1986b. Spectrin, red cell shape and deformability. II. The antagonistic action of spectrin and sialic acid residues in determining membrane curvature in genetic spectrin deficiency in mice. Blut 52:149-164.

    Article  Google Scholar 

  74. Schmidt, R., F. Lang, and G. Thews. 2005. Physiologie des Menschen mit Pathophysiologie. Springer Verlag.

    Google Scholar 

  75. Shi, Y.D., G. Artmann, R. Agosti, and E. Longhini. 1998. A modified Casson equation to characterize blood rheology for hypertension. Clin. Hemorheol. Microcirc. 19:115-127.

    Google Scholar 

  76. Silva, J.E. 2006. Thermogenic mechanisms and their hormonal regulation. Physiol Rev. 86:435-464.

    Article  Google Scholar 

  77. Simpson, S. and J.J. Galbraith. 1905. Observations on the normal temperatures of the monkey and its diurnal variation, and on the effects of changes in the daily routine in this variation. Transaction of the royal society of Edinburgh 45:65-104.

    Google Scholar 

  78. Soupene, E. and F.A. Kuypers. 2006. Identification of an erythroid ATP-dependent aminophospholipid transporter. Br. J. Haematol. 133:436-438.

    Article  Google Scholar 

  79. Staat, M. Biomechanical considerations on Red Blood Cell aspiration into narrow micropipettes. 6-6-2007. 6-6-2007. Personal Communication

    Google Scholar 

  80. Stadler, A. M., Zerlin, K. F., Digel, I., Artmann, G. M., Embs, J. P., Buldt, G., and Zaccai, G. Dynamics of hemoglobin and water in human red blood cells and concentrated hemoglobin solutions. Abstract 128. 14-7-2007. London, European Biophysics Congress. 14-7-2007. Conference Proceeding

    Google Scholar 

  81. Temiz, A., O.K. Baskurt, C. Pekcetin, F. Kandemir, and A. Gure. 2000. Leukocyte activation, oxidant stress and red blood cell properties after acute, exhausting exercise in rats. Clin. Hemorheol. Microcirc. 22:253-259.

    Google Scholar 

  82. Todd, J.C., III and D.L. Mollitt. 1994. Sepsis-induced alterations in the erythrocyte membrane. Am. Surg. 60:954-957.

    Google Scholar 

  83. Tominaga, M. 2004. [Molecular mechanisms of thermosensation]. Nippon Yakurigaku Zasshi 124:219-227.

    Google Scholar 

  84. Tremmel, I.G., E. Weis, and G.D. Farquhar. 2005. The influence of protein-protein interactions on the organization of proteins within thylakoid membranes. Biophys. J. 88:2650-2660.

    Article  Google Scholar 

  85. Veldkamp, W.B. and J.R. Votano. 1980. Temperature dependence of macromolecular interactions in dilute and concentrated hemoglobin solutions. Biopolymers 19:111-124.

    Article  Google Scholar 

  86. Vitkup, D., D. Ringe, G.A. Petsko, and M. Karplus. 2000. Solvent mobility and the protein ’glass’ transition. Nat. Struct. Biol. 7:34-38.

    Article  Google Scholar 

  87. Walz, T., T. Hirai, K. Murata, J.B. Heymann, K. Mitsuoka, Y. Fujiyoshi, B.L. Smith, P. Agre, and A. Engel. 1997. The three-dimensional structure of aquaporin-1. Nature 387:624-627.

    Article  Google Scholar 

  88. Wenzel, J.J., A. Piehler, and W.E. Kaminski. 2007. ABC A-subclass proteins: gatekeepers of cellular phospho- and sphingolipid transport. Front Biosci. 12:3177-3193.

    Article  Google Scholar 

  89. Whittow, C. 1971. Comparative physiology of thermoregulation. Academic Press, New York and London.

    Google Scholar 

  90. Yan, Y.B., Q. Wang, H.W. He, X.Y. Hu, R.Q. Zhang, and H.M. Zhou. 2003. Two-dimensional infrared correlation spectroscopy study of sequential events in the heat-induced unfolding and aggregation process of myoglobin. Biophys J 85:1959-1967.

    Google Scholar 

  91. Yan, Y.B., R.Q. Zhang, and H.M. Zhou. 2002. Biphasic reductive unfolding of ribonuclease A is temperature dependent. Eur J Biochem. 269:5314-5322.

    Article  Google Scholar 

  92. Yokoyama, K., T. Terao, and T. Osawa. 1978. Membrane receptors of human erythrocytes for bacterial lipopolysaccharide (LPS). Jpn. J. Exp. Med. 48:511-517.

    Google Scholar 

  93. Zefirova, T.P., A.N. Glebov, E.N. Gur’ev, R.S. Mavliautdinov, and O.I. Tarasov. 1991. [Nuclear magnetic relaxation of aqueous solutions of proteins, plasma, erythrocytes, and blood]. Biull. Eksp. Biol. Med. 112:378-381.

    Google Scholar 

  94. Zerlin, K.F., N. Kasischke, I. Digel, C. Maggakis-Kelemen, A.A. Temiz, D. Porst, P. Kayser, P. Linder, and G.M. Artmann. 2007. Structural transition temperature of hemoglobins correlates with species’ body temperature. Eur Biophys J 37:1-10.

    Article  Google Scholar 

  95. Zheng, J.M. and G.H. Pollack. 2003. Long-range forces extending from polymer-gel surfaces. Phys. Rev. E. Stat. Nonlin. Soft. Matter Phys. 68:031408.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Artmann, G., Zerlin, K., Digel, I. (2008). Hemoglobin Senses Body Temperature. In: Artmann, G., Chien, S. (eds) Bioengineering in Cell and Tissue Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75409-1_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-75409-1_17

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-75408-4

  • Online ISBN: 978-3-540-75409-1

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics