Skip to main content


We’d like to understand how you use our websites in order to improve them. Register your interest.

Solute-dependent activation of cell motility in strongly hypertonic solutions in Dictyostelium discoideum, human melanoma HTB-140 cells and walker 256 carcinosarcoma cells


Published data concerning the effects of hypertonicity on cell motility have often been controversial. The interpretation of results often rests on the premise that cell responses result from cell dehydration, i.e. osmotic effects. The results of induced hypertonicity on cell movement of Dictyostelium discoideum amoebae and human melanoma HTB-140 cells reported here show that: i) hypertonic solutions of identical osmolarity will either inhibit or stimulate cell movement depending on specific solutes (Na+ or K+, sorbitol or saccharose); ii) inhibition of cell motility by hypertonic solutions containing Na+ ions or carbohydrates can be reversed by the addition of calcium ions; iii) various cell types react differently to the same solutions, and iv) cells can adapt to hypertonic solutions. Various hypertonic solutions are now broadly used in medicine and to study modulation of gene expression. The observations reported suggest the need to examine whether the other responses of cells to hypertonicity can also be based on the solute-dependent cell responses besides cell dehydration due to the osmotic effects.



balanced salt solution


coefficient of movement efficiency


ethylene glycol bis(β-aminoethyl ether)-N,N-tetraacetic acid


human melanoma cell line


standard error of the mean


tetramethyl rhodamine iso-thiocyanate


  1. 1.

    Zischka, H., Oehme, F., Pintsch, T., Ott, A., Keller, H., Kellermann, J. and Schuster, S.C. Rearrangement of cortex proteins constitutes and osmoprotective mechanism in Dictyostelium. EMBO J. 18 (1999) 4241–4249.

  2. 2.

    Erickson, G.R., Alexopoulos, L.G. and Guilak, F. Hyper-osmotic stress induces volume change and calcium transients in chondrocytes by transmembrane, phospholipids, and G-protein pathways. J. Biomech. 34 (2001) 1527–1535.

  3. 3.

    Cai, Q., Michea, L., Andrews, P., Zhang, Z., Rocha, G., Dmitrieva, N. and Burg M.B. Rate of increase of osmolarity determined osmotic tolerance of mouse inner medullary epithelial cells. Am. J. Physiol. Renal Physiol. 283 (2002) F792–798.

  4. 4.

    Mavrogonatou, E. and Kletsas, D. High osmolarity activates the G1 and G2 cell cycle checkpoints and affects the DNA integrity of nucleus pulposus intervertebral disc cells triggering an enhanced DNA repair response. DNA Repair (Amst) 8 (2009) 930–943.

  5. 5.

    Kerwin, A.J., Schinco, M.A., Tepas, J.J., Renfro, W.H., Vitarbo, E.A., and Muehlberger, M. The use of 23.4% hypertonic saline for the management of elevated intracranial pressure in patients with severe traumatic brain injury: A pilot study. J. Trauma 67 (2009) 277–282.

  6. 6.

    Loram, L., Horwitz, E. and Bentlley, A. Gender and site of injection do not influence intensity of hypertonic saline-induced muscle pain in healthy volunteers. Man Ther. 14 (2009) 526–530.

  7. 7.

    Vinzenzi, R., Cepeda, L.A., Pirani, W.M., Sannomyia, P., Rocha-e-Silvia, M. and Cruz, R. Small volume resuscitation with 3% hypertonic saline solution decrease inflammatory response and attenuates end organ damage after controlled hemorrhagic shock. Am. J. Surg. 198 (2009) 407–414.

  8. 8.

    Burg, M.B., Kwon, E.D. and Kültz, D. Regulation of gene expression by hypertonicity. Annu. Rev. Physiol. 59 (1997) 437–455.

  9. 9.

    Maallem, S., Wierinckx, A., Lachuer, J., Kwon, M.H. and Tappaz, M.L. Gene expression profiling in brain following acute systemic hypertonicity: novel genes possibly involved in osmoadaptation. J. Neurochem 105 (2008) 1198–1211.

  10. 10.

    Oster, G.F. and Perelson, A.S. The physics of cell motility. J. Cell Sci. Suppl.8 (1987) 35–54.

  11. 11.

    Fedier, A. and Keller, H.U. Suppression of bleb formation, locomotion, and polarity of Walker carcinosarcoma cells by hypertonic media correlates with cell volume reduction but not with changes in the F-actin content. Cell. Motil. Cytoskeleton 37 (1997) 326–337.

  12. 12.

    Schachtschabel, D.O. and Foley, G.E. Serial cultivation of Ehrlich ascites tumor cells in hypertonic media. Exp. Cell Res. 70 (1972) 317–324.

  13. 13.

    Korohoda, W. and Stockem, W. Experimentally induced destabilization of the cell membrane and cell surface activity in Amoeba proteus. Cytobiologie (Europ. J. Cell Biol.) 12 (1975) 93–110.

  14. 14.

    Erickson, G.R., Alexopoulos, L.G. and Guilak F. Hyper-osmotic stress induces volume change and calcium transients in chemocytes by transmembrane, phospholipids, and G-protein pathways. J. Biomech. 34 (2002) 1527–1535.

  15. 15.

    Yoshida, K. and Inouye, K. Myosin II -dependent cylindrical protrusions induced by quinine in Dictystelium: antagonizing effects of actin polymerization at the leading edge. J. Cell Sci. 114 (2001) Pt 11 2155–2165.

  16. 16.

    Franz, C.M., Jones, G.E. and Ridley A.J. Cell migration in development and disease. Dev. Cell 2 (2002) 153–158.

  17. 17.

    Stracke, M.L., Aznavoorian, S.A., Beckner, M.E., Liotta, L.A. and Schiffmann, E. Cell motility, a principal requirement for metastasis. EXS 59 (1991) 147–162.

  18. 18.

    Condeelis, J., Singer, R.H. and Segall, J.E. The great escape: When cancer cells hijack the genes for chemotaxis and motility. Annu. Rev. Cell. Dev. Biol. 21 (2005) 695–718.

  19. 19.

    Yamaguchi, H. and Condeelis, J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim. Biophys. Acta 1773 (2007) 642–652.

  20. 20.

    Varani, J. Control of cell motility during tissue invasion. In: Kaiser, H.E. and Nasir, A. editors. Selected Aspects of Cancer progression: Metastasis, Apoptosis and Immune Response. Springer Sci. Buisness Media BV (2008) 11–19.

  21. 21.

    Korohoda, W., Madeja, Z. and Sroka, J. Diverse chemotactic responses of Dictyostelium discoideum amoebae in the developing (temporal) and stationary (spatial) concentration gradients of folic acid, cAMP, Ca(2+) and Mg(2+). Cell Motil. Cytoskeleton 53 (2002) 1–25.

  22. 22.

    Waligórska, A., Wianecka-Skoczeń, M. and Korohoda, W. Motile activities of Dictyostelium discoideum differ from those in Protista or vertebrate animal cells. Folia Biol. (Kraków) 55 (2007) 87–93.

  23. 23.

    Sroka, J., Kamiński, R., Michalik, M., Madeja, Z., Przestalski, S. and Korohoda, W. The effect of triethyllead on the motile activity of Walker 256 carcinosarcoma cells. Cell. Mol. Biol. Lett. 9 (2004) 15–30.

  24. 24.

    Bereiter-Hahn, J. and Kajstura, J. Scanning microfluorometric measurement of TRITC-phalloidin labelled F-actin. Dependence of F-actin content on density of normal and transformed cells. Histochemistry 90 (1988) 271–276.

  25. 25.

    Kajstura, J. and Bereiter-Hahn, J. Scanning microfluorometric measurement of immunofluorescently labelled microtubules in cultured cells. Dependence of microtubule content on cell density. Histochemistry 88 (1987) 53–55.

  26. 26.

    Waligórska, A., Wianecka-Skoczeń, M., Nowak, P. and Korohoda, W. Some difficulties in research into cell motile activity under isotropic conditions. Folia Biol (Krakow) 55 (2007) 9–16.

  27. 27.

    Korohoda, W. and Madeja, Z. Contact of sarcoma cells with aligned fibroblasts accelerates their displacement: computer — assisted analysis of tumor cell locomotion in coculture. Biochem. Cell. Biol. 75 (1997) 263–276.

  28. 28.

    Erickson, C.A. and Nuccitelli, R. Embryonic fibroblast motility and orientation can be influenced by physiological electric fields. J. Cell Biol. 98 (1984) 296–307.

  29. 29.

    Wójciak-Stothard, B., Madeja, Z., Korohoda, W., Curtis, A.S.G. and Wilkinson, H. Activation of macrophage-like cells by multiple grooved substrata. Topographical control of cell behaviour. Cell Biol. Int. 19 (1995) 485–490.

  30. 30.

    Gail, M. Time lapse studies on the motility of fibroblasts in tissue culture. In: Ciba Found. Symp.14, (Porter, R., Fitzsimons, D.W. Eds.) Locomotion of Tissue Cells. Elsevier, Excperta Medica, North-Holland, Amsterdam, London, New York, (1973) 287–310.

  31. 31.

    Sroka, J., Kordecka, A., Włosiak, P., Madeja, Z. and Korohoda, W. Separation methods for isolation of human polymorphonuclear leukocytes affect their motile activity. Eur. J. Cell Biol. 88 (2009) 531–539.

  32. 32.

    Kruyt, H.R. and Overbeek, J.T.G. An Introduction to Physical Chemistry. W. Heinemann Ltd: London and Tonbridge; 1960.

  33. 33.

    Barrow, G.M. Physical Chemistry, McGraw-Hill New York, 1961.

  34. 34.

    Katchalsky, A. and Curran, P.F. Nonequilibrium thermodynamics in biophysics. Harvard University Press, Cambridge, Massachusetts, (1965) 1–248.

  35. 35.

    Szydłowska, H., Zasporowska, E., Kuszlik-Jochym, K., Korohoda. W. and Branny, J. Membranolytic activity of detergents as studiem with cell viability tests. Folia Histochem. Cytochem. 16 (1978) 69–78.

  36. 36.

    Ling, G.N. A Physical Theory of the Living State. The Association Induction Hypothesis. Blaisdell Publ. Co. New York; 1962.

  37. 37.

    Van Duijn, B., Vogelzang, S.A., Ypey, D.L., Van der Molen, L.G. and Van Haastert, P.J. Normal chemotaxis in Dictyostelium discoideum cells with a depolarized plasma membrane potential. J. Cell Sci. 95 (1990) (Pt 1) 177–183.

  38. 38.

    Wessels, D., Titus, M. and Soll, D.R. A Dictyostelium myosin I plays a crucial role in regulating the frequency of pseudopods formed on the substratum. Cell Motil. Cytoskeleton 33 (1996) 64–79.

  39. 39.

    Stracke, M.L., Aznavoornian, S.A., Beckner, M.E., Liotta, L.A. and Schiffmann E. Cell motility, a principal requirement for metastasis. EXS 59 (1991) 147–162.

  40. 40.

    Quiñones, L.G. and Garcia-Castro, I. Characterization of human melanoma cell lines according to their migratory properties in vitro. In Vitro Cell. Dev. Biol. Anim. 40 (2004) 35–42.

  41. 41.

    Lewis, L., Barrandon, Y., Green, H. and Albrecht-Buehler, G. The reorganization of microtubules and microfilaments in differentiating keratinocytes. Differentiation 36 (1987) 228–233.

  42. 42.

    Blasé, C., Becker, D., Kappel, S. and Bereiter-Hahn, J. Microfilament dynamics during HaCat cell volume regulations. Eur. J. Cell Biol. 88 (2009) 131–139.

  43. 43.

    Schmitz, H.D. and Bereiter-Hahn, J. GFP associates with microfilaments in fixed cells. Histochem. Cell Biol. 116 (2001) 89–94.

  44. 44.

    Crowe, J.H., Whittam, M.A., Chapman, D. and Crowe, L.M. Interactions of phospholipids monolayers with carbohydrates. Biochim. Biophys. Acta 769 (1984) 151–159.

  45. 45.

    Clegg, J.S., Gallo, J. and Gordon, E. Some structural, biochemical and biophysical characteristics of L-929 cells growing in the presence of hyperosmotic sorbitol concentration. Exp. Cell Res. 163 (1986) 35–46.

  46. 46.

    Rand, R.P., Parsegian, V.A. and Rau, D.C. Intracellular osmotic action. Cell. Mol. Life Sci. 57 (2000) 1018–1032.

  47. 47.

    Dall’Asta, V., Bussolati, O., Sala, R., Parolari, A., Alamanni, F., Biglioli, P. and Gazzol G.C. Amino acids are compatible osmolytes for volume recovery after hypertonic shrinkage in vascular endothelial cells. Am. J. Physiol. 276 (1999) C865–872.

  48. 48.

    Schaffer, S., Takahashi, K. and Azuma J. Role of osmoregulation in the actions of taurine. Amino Acids 19 (2000) 527–546.

  49. 49.

    Schuster, S.C., Noegel, A.N., Oehme, F., Gerisch, G. and Simon, M.I. The hybrid histone kinase Dok A is part of the osmotic response system of Dictyostelium. EMBO J. 15 (1996) 3880–3889.

  50. 50.

    Steck, T.L., Chiaraviglio, L. and Meredith, S. Osmotic homeostasis in Dictyostelium discoideyn: excretion of amino acids and ingested solutes. J. Eukaryot. Microbiol. 44 (1997) 503–510.

  51. 51.

    Guthrie, H.D., Liu, J. and Crister, J.K. Osmotic tolerance limits and effects of osmoprotectants on motility of bovine spermatozoa. Biol. Reprod. 67 (2002) 1811–1816.

  52. 52.

    Heilbrunn, L.V. and Daugherty, K. The action of sodium, potassium, calcium and magnesium ions on the plasmagel of Amoeba proteus. Physiol. Zool. 5 (1932) 254–274.

  53. 53.

    Thiel, M., Buessecker, F, Eberhardt, K, Chouker, A., Setzer, F., Kreimeier, U., Arforst, K.E., Peter, K. and Messmer K. Effects of hypertonic saline on expression of human polymorphonuclear leukocyte adhesion molecules. J. Leukoc. Biol. 70 (2001) 261–273.

  54. 54.

    Bryszewska, M. and Epand, R.M. Effects of sugar alcohols and disaccharides in inducing the hexagonal phase and altering membrane properties: implications for diabetes mellitus. Biochim. Biophys. Acta 943 (1988) 485–492.

  55. 55.

    Wyckoff, J.B., Segall, J.E. and Condeelis, J.S. The collection of the motile population of cells from a living tumor. Cancer Res. 60 (2000) 5401–5404.

Download references

Author information



Corresponding author

Correspondence to Włodzimierz Korohoda.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Korohoda, W., Kucia, M., Wybieralska, E. et al. Solute-dependent activation of cell motility in strongly hypertonic solutions in Dictyostelium discoideum, human melanoma HTB-140 cells and walker 256 carcinosarcoma cells. Cell Mol Biol Lett 16, 412–430 (2011).

Download citation

Key words

  • Cell motility activation
  • Hypertonicity
  • Solute-dependent
  • Membrane interaction