Modelling Approach to Enzymatic pH Oscillators in Giant Lipid Vesicles

  • Ylenia Miele
  • Tamás BánságiJr.
  • Annette F. Taylor
  • Federico RossiEmail author
Part of the Lecture Notes in Bioengineering book series (LNBE)


The urease-catalyzed hydrolysis of urea can display feedback driven by base production (NH3) resulting in a switch from acidic to basic pH under non-buffered conditions. Thus, this enzymatic reaction is a good candidate for investigation of chemical oscillations or bistability. In order to determine the best conditions for oscillations, a two-variable model was initially derived in which acid and urea were supplied at rates k H and k S from an external medium to an enzyme-containing compartment. Oscillations were theoretically observed providing the necessary condition that k H > k S was met. To apply this model, we devised an experimental system able to ensure the fast transport of acid compared to that of urea. In particular, by means of the droplet transfer method, we encapsulated the enzyme, together with a proper pH probe, in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) based liposomes, where differential diffusion of H+ and urea is ensured by the different permeability (P m) of the membrane to the two species. Here we present an improved theoretical model that accounts for the products transport and for the probe hydrolysis, to obtain a better guidance for the experiments.


Enzymatic oscillators Urea-urease reaction Lipid vesicles pH oscillators 



Y.M. and F.R. were supported by the grants ORSA158121 and ORSA167988 funded by the University of Salerno (FARB ex 60%). The authors acknowledge the support through the COST Action CM1304 (Emergence and Evolution of Complex Chemical Systems).


  1. 1.
    Nicolis, G., Prigogine, I.: Self-organization in nonequilibrium systems. Wiley, New York (1977)zbMATHGoogle Scholar
  2. 2.
    Orban, M., Kurin-Csorgei, K., Epstein, I.R.: pH-Regulated chemical oscillators. Acc. Chem. Res. 48(3), 593–601 (2015)CrossRefGoogle Scholar
  3. 3.
    Takeoka, Y., Watanabe, M., Yoshida, R.: Self-sustaining peristaltic motion on the surface of a porous gel. J. Am. Chem. Soc. 125(44) (2003) 13320–13321 pH Oscillators in GVs 11Google Scholar
  4. 4.
    Paul, A.: Observations of the effect of anionic, cationic, neutral, and zwitterionic surfactants on the Belousov-Zhabotinsky reaction. J. Phys.Chem. B 109(19), 9639–9644 (2005)CrossRefGoogle Scholar
  5. 5.
    Rossi, F., Varsalona, R., Liveri, M.L.T.: New features in the dynamics of a ferroincatalyzed Belousov-Zhabotinsky reaction induced by a zwitterionic surfactant. Chem. Phys. Lett. 463(4–6), 378–382 (2008)CrossRefGoogle Scholar
  6. 6.
    Jahan, R.A., Suzuki, K., Mahara, H., Nishimura, S., Iwatsubo, T., Kaminaga, A., Yamamoto, Y., Yamaguchi, T.: Perturbation mechanism and phase transition of AOT aggregates in the Fe(II)[batho(SO3)2]3—catalyzed aqueous Belousov-Zhabotinsky reaction. Chem. Phys. Lett. 485(4–6), 304–308 (2010)CrossRefGoogle Scholar
  7. 7.
    Rossi, F., Liveri, M.L.T.: Chemical self-organization in self-assembling biomimetic systems. Ecol. Model. 220(16), 1857–1864 (2009)CrossRefGoogle Scholar
  8. 8.
    Sciascia, L., Rossi, F., Sbriziolo, C., Liveri, M.L.T., Varsalona, R.: Oscillatory dynamics of the Belousov-Zhabotinsky system in the presence of a self-assembling nonionic polymer. Role of the reactants concentration. Phys. Chem. Chem. Phys. 12(37), 11674–11682 (2010)CrossRefGoogle Scholar
  9. 9.
    Rossi, F., Varsalona, R., Marchettini, N., Turco Liveri, M.L.: Control of spontaneous spiral formation in a zwitterionic micellar medium. Soft Matter 7, 9498 (2011)CrossRefGoogle Scholar
  10. 10.
    Vanag, V.K., Epstein, I.R.: Pattern formation in a tunable medium: The Belousov-Zhabotinsky reaction in an aerosol OT microemulsion. Phys. Rev. Lett. 87(22), 228301–4 (2001)Google Scholar
  11. 11.
    Toiya, M., Vanag, V.K., Epstein, I.R.: Diffusively coupled chemical oscillators in a microfluidic assembly. Angew. Chem. Int. Ed. 47(40), 7753–7755 (2008)CrossRefGoogle Scholar
  12. 12.
    Rossi, F., Vanag, V.K., Epstein, I.R.: Pentanary cross-diffusion in water-in—oil microemulsions loaded with two components of the Belousov-Zhabotinsky reaction. Chem. Eur. J. 17(7), 2138–2145 (2011)CrossRefGoogle Scholar
  13. 13.
    Tompkins, N., Li, N., Girabawe, C., Heymann, M., Ermentrout, G.B., Epstein, I.R., Fraden, S.: Testing turing’s theory of morphogenesis in chemical cells. Proc. Natl. Acad. Sci. 111(12), 4397–4402 (2014)CrossRefGoogle Scholar
  14. 14.
    Walde, P., Umakoshi, H., Stano, P., Mavelli, F.: Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators. Chem. Commun. 50(71), 10177–10197 (2014)CrossRefGoogle Scholar
  15. 15.
    Tomasi, R., Noel, J.M., Zenati, A., Ristori, S., Rossi, F., Cabuil, V., Kanoufi, F., Abou-Hassan, A.: Chemical communication between liposomes encapsulating a chemical oscillatory reaction. Chem. Sci. 5(5), 1854–1859 (2014)CrossRefGoogle Scholar
  16. 16.
    Rossi, F., Zenati, A., Ristori, S., Noel, J.M., Cabuil, V., Kanoufi, F., Abou-Hassan, A.: Activatory coupling among oscillating droplets produced in microfluidic based devices. Int. J. Unconventional Comput. 11(1), 23–36 (2015)Google Scholar
  17. 17.
    Torbensen, K., Rossi, F., Pantani, O.L., Ristori, S., Abou-Hassan, A.: Interaction of the Belousov-Zhabotinsky reaction with phospholipid engineered membranes. J. Phys. Chem. B 119(32), 10224–10230 (2015)CrossRefGoogle Scholar
  18. 18.
    Stockmann, T.J., Noël, J.M., Ristori, S., Combellas, C., Abou-Hassan, A., Rossi, F., Kanoufi, F.: Scanning electrochemical microscopy of Belousov-Zhabotinsky reaction: how confined oscillations reveal short lived radicals and auto-catalytic species. Anal. Chem. 87(19), 9621–9630 (2015)CrossRefGoogle Scholar
  19. 19.
    Taylor, A.F., Tinsley, M.R.,Wang, F., Huang, Z., Showalter, K.: Dynamical quorum sensing and synchronization in large populations of chemical oscillators. Science 323(5914), 614–617 (2009)Google Scholar
  20. 20.
    Rossi, F., Ristori, S., Marchettini, N., Pantani, O.L.: Functionalized clay microparticles as catalysts for chemical oscillators. J. Phys. Chem. C 118(42), 24389–24396 (2014)CrossRefGoogle Scholar
  21. 21.
    Hu, G., Pojman, J.A., Scott, S.K., Wrobel, M.M., Taylor, A.F.: Base-catalyzed feedback in the urea-urease reaction. J. Phys. Chem. B 114(44), 14059–14063 (2010)CrossRefGoogle Scholar
  22. 22.
    Wrobel, M.M., Bánsági, T., Scott, S.K., Taylor, A.F., Bounds, C.O., Carranza, A., Pojman, J.A.: pH wave-front propagation in the urea-urease reaction. Biophys. J. 103(3), 610–615 (2012)CrossRefGoogle Scholar
  23. 23.
    Miele, Y., Bánsági, T., Taylor, A.F., Stano, P., Rossi, F.: Engineering enzyme-driven dynamic behaviour in lipid vesicles. In Rossi, F., Mavelli, F., Stano, P., Caivano, D. (eds.): Advances in artificial life, evolutionary computation and systems chemistry. Number 587 in communications in computer and information science, pp. 197–208. Springer International Publishing (2015)Google Scholar
  24. 24.
    Stingl, K., Altendorf, K., Bakker, E.P.: Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis? Trends Microbiol. 10(2), 70–74 (2002)CrossRefGoogle Scholar
  25. 25.
    Muzika, F., Bansagi, T., Schreiber, I., SchreiberovAą, L., Taylor, A.F.: A bistable switch in pH in urease-loaded alginate beads. Chem. Commun. (Cambridge, England) 50(76), 11107–11109 (2014)Google Scholar
  26. 26.
    Lasic, D.D., Barenholz, Y.: Handbook of nonmedical applications of liposomes: theory and basic sciences, vol. 1. CRC Press (1996)Google Scholar
  27. 27.
    Paula, S., Volkov, A., Van Hoek, A., Haines, T., Deamer, D.W.: Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness. Biophys. J 70(1), 339 (1996)CrossRefGoogle Scholar
  28. 28.
    Pautot, S., Frisken, B.J., Weitz, D.A.: Production of unilamellar vesicles using an inverted emulsion. Langmuir 19(7), 2870–2879 (2003)CrossRefGoogle Scholar
  29. 29.
    Carrara, P., Stano, P., Luisi, P.L.: Giant vesicles colonies: a model for primitive cell communities. ChemBioChem 13(10), 1497–1502 (2012)CrossRefGoogle Scholar
  30. 30.
    Stano, P., Wodlei, F., Carrara, P., Ristori, S., Marchettini, N., Rossi, F.: Approaches to molecular communication between synthetic compartments based on encapsulated chemical oscillators. In Pizzuti, C., Spezzano, G., (eds.): Advances in Artificial Life and Evolutionary Computation. Number 445 in Communications in Computer and Information Science, pp. 58–74. Springer International Publishing (2014)Google Scholar
  31. 31.
    Ermentrout, B.: Simulating, analyzing, and animating dynamical systems: a guide to XPPAUT for researchers and students, vol. 14. Siam (2002)Google Scholar
  32. 32.
    Mathai, J.C., Sprott, G.D., Zeidel, M.L.: molecular mechanisms of water and solute transport across archaebacterial lipid membranes. J. Biol. Chem. 276(29), 27266–27271 (2001)CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Ylenia Miele
    • 1
  • Tamás BánságiJr.
    • 2
  • Annette F. Taylor
    • 2
  • Federico Rossi
    • 1
    Email author
  1. 1.Department of Chemistry and BiologyUniversity of SalernoFiscianoItaly
  2. 2.Department of Chemical and Biological EngineeringUniversity of SheffieldSheffieldUK

Personalised recommendations