Skip to main content


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

Exploring the binding dynamics of BAR proteins


We used a continuum model based on the Helfrich free energy to investigate the binding dynamics of a lipid bilayer to a BAR domain surface of a crescent-like shape of positive (e.g. I-BAR shape) or negative (e.g. F-BAR shape) intrinsic curvature. According to structural data, it has been suggested that negatively charged membrane lipids are bound to positively charged amino acids at the binding interface of BAR proteins, contributing a negative binding energy to the system free energy. In addition, the cone-like shape of negatively charged lipids on the inner side of a cell membrane might contribute a positive intrinsic curvature, facilitating the initial bending towards the crescent-like shape of the BAR domain. In the present study, we hypothesize that in the limit of a rigid BAR domain shape, the negative binding energy and the coupling between the intrinsic curvature of negatively charged lipids and the membrane curvature drive the bending of the membrane. To estimate the binding energy, the electric potential at the charged surface of a BAR domain was calculated using the Langevin-Bikerman equation. Results of numerical simulations reveal that the binding energy is important for the initial instability (i.e. bending of a membrane), while the coupling between the intrinsic shapes of lipids and membrane curvature could be crucial for the curvature-dependent aggregation of negatively charged lipids near the surface of the BAR domain. In the discussion, we suggest novel experiments using patch clamp techniques to analyze the binding dynamics of BAR proteins, as well as the possible role of BAR proteins in the fusion pore stability of exovesicles.





insulin receptor tyrosine kinase substrate p53


  1. 1.

    Farsad, K., Ringstad, N., Takei, K., Floyd, S.R., Rose, K. and De Camilli P. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J. Cell Biol. 105 (2001) 193–200.

  2. 2.

    Tarricone, C., Xiao, B., Justin, N., Walker, P.A., Rittinger, K., Gamblin, S.J. and Smerdon, S.J. The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways. Nature 411 (2001) 215–219.

  3. 3.

    Zimmerberg, Y.J. and Kozlov, M.M. How proteins produce cellular curvature. Nat. Rev. Mol. Cell Biol. 7 (2006) 9–19.

  4. 4.

    Veksler, A. and Gov, N.S. Phase transitions of the coupled membranecytoskeleton modify cellular shape. Biophys. J. 11 (2007) 3798–3810.

  5. 5.

    Frost, A., Unger, V.M. and De Camilli, P. The BAR Domain Superfamily: Membrane-Molding Macromolecules. Cell 137 (2009) 191–196.

  6. 6.

    Wang, Q., Navarro, M.V., Peng, G., Molinelli, E., Lin-Goh, S. and Judson, B.L., Rajashankar, K.R. and Sondermann, H. Molecular mechanism of membrane constriction and tubulation mediated by the F-BAR protein Pacsin/Syndapin. Proc. Nat. Acad. Sci. USA 106 (2009) 12700–12705.

  7. 7.

    Peter, B.J., Kent, H.M., Mills, I.G., Vallis, Y., Butler, P.J., Evans, P.R. and McMahon, H.T. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303 (2004) 495–499.

  8. 8.

    Itoh, T. and De Camilli, P. BAR, F-BAR (EFC) and ENTH/ANTH domains in the regulation of membrane-cytosol interfaces and membrane curvature. Biochim. Biophys. Acta 1761 (2006) 897–912.

  9. 9.

    Heath, R.J.W. and Insall, R.H. F-BAR domains: multifunctional regulators of membrane curvature. J. Cell Sci. 121 (2008) 1951–1954.

  10. 10.

    Shimada, A., Takano, K., Shirouzu, M., Hanawa-Suetsugu, K., Terada, T., Toyooka, K., Umehara, T., Yamamoto, M., Yokoyama, S. and Suetsugu, S. Mapping of the basic amino-acid residues responsible for tubulation and cellular protrusion by the EFC/F-BAR domain of pacsin2/syndapin II. FEBS Lett. 584 (2010) 1111–1118.

  11. 11.

    Zimmerberg, J. and McLaughlin, S. Membrane curvature: How BAR domains bend bilayers. Curr. Biol. 14 (2004) 250–252.

  12. 12.

    Iglič, A., Slivnik, T. and Kralj-Iglič, V. Elastic properties of biological membranes influenced by attached proteins. J. Biomech. 40 (2007) 2492–2500.

  13. 13.

    Kabaso, D., Shlomovitz, R., Auth, T., Lew, V.L. and Gov, N.S. Curling and local shape changes of red blood cell membranes driven by cytoskeletal reorganization. Biophys. J. 99 (2010) 808–816.

  14. 14.

    Kabaso, D., Gongadze, E., Perutkova, S., Kralj-Iglič, V., Matschegewski, C., Beck, U., van Rienen, U. and Iglič, A. Mechanics and electrostatics of the interactions between osteoblasts and titanium surface. Comp. Meth. Biomech. Biomed. Eng. (2011) in print.

  15. 15.

    Kabaso, D., Lokar, M., Kralj-Iglič, V., Veranič, P. and Iglič, A. Temperature, cholera toxin-B and degree of malignant transformation are factors that influence formation of membrane nanotubes in urothelial cancer cell line. Int. J. Nanomed. 6 (2011) 495–509.

  16. 16.

    Kralj-Iglič, V., Heinrich, V., Svetina, S. and Zeks, B. Free energy of closed membrane with anisotropic inclusions. Eur. Phys. J. B. 10 (1999) 5–8.

  17. 17.

    Božič, B., Kralj-Iglič, V. and Svetina, S. Coupling between vesicle shape and lateral distribution of mobile membrane inclusion. Phys. Rev. E 73 (2006) 041915.

  18. 18.

    Cai, W. and Lubensky, T.C. Covariant hydrodynamics of fluid membranes. Phys. Rev. Lett. 73 (1994) 1186–1189.

  19. 19.

    Helfrich, W. Elastic properties of lipid bilayers: theory and possible experiments. Z. Naturforsch. C 28 (1973) 693–703.

  20. 20.

    Gongadze, E., van Rienen, U., Kralj-Iglič, V. and Iglič, A. Langevin Poisson-Boltzmann equation: point-like ions and water dipoles near charged membrane surface. Gen. Physiol. Biophys. 30 (2011) in print.

  21. 21.

    Iglič, A., Gongadze, E. and Bohinc, K. Excluded volume effect and orientational ordering near charged surface in solution of ions and Langevin dipoles. Bioelectrochemistry 79 (2010) 223–227.

  22. 22.

    Gongadze, E, Bohinc, K., van Rienen, U., Kralj-Iglič, V. and Iglič, A. Spatial variation of permittivity near a charged membrane in contact with electrolyte solution, in: Advances in planar lipid bilayers and liposomes (Iglič, A. Ed.) 11th volume, Elsevier, 2010, 101–126.

  23. 23.

    Hamill, O., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Eur. J. Phys. 391 (1981) 85–100.

  24. 24.

    Hille, B. Gating Mechanisms: Kinetic Thinking. In: Ionic Channels of Excitable Membranes (1992) 575–603.

  25. 25.

    Sikdar, S.K., Zorec, R. and Mason, W.T. cAMP directly facilitates Cainduced exocytosis in bovine lactotrophs. FEBS Lett. 273 (1990) 150–154.

  26. 26.

    Rupnik, M. and Zorec, R. Cytosolic chloride ions stimulate Ca2+-induced exocytosis in melanotrophs. FEBS Lett. 303 (1992) 221–223.

  27. 27.

    Kreft, M. and Zorec, R. Cell-attached measurements of attofarad capacitance steps in rat melanotrophs. Pflügers Archiv. 434 (1997) 212–214.

  28. 28.

    Fosnaric, M., Iglič, A., Kroll, D. and May, S. Monte Carlo simulations of complex formation between a mixed fluid vesicle and a charged colloid. J. Chem. Phys. 131 (2009) 105103.

  29. 29.

    Khelashvili, G., Harries, D. and Weinstein, H. Modeling membrane deformations and lipid demixing upon protein-membrane interaction: The BAR dimer adsorption. Biophys. J. 97 (2009) 1626–1635.

  30. 30.

    Jorgačevski, J., Fošnarič, M., Vardjan, N., Stenovec, M., Potokar, M., Kreft, M., Kralj-Iglič, V., Iglič, A. and Zorec, R. Fusion pore stability of peptidergic vesicles. Mol. Membr. Biol. 27 (2010) 65–80.

  31. 31.

    Neher, E. and Marty, A. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc. Natl. Acad. Sci. USA 79 (1982) 6712–6716.

  32. 32.

    Darios, F., Wasser, C., Shakirzyanova, A., Giniatullin, A., Goodman, K., Munoz-Bravo, J.L., Raingo, J., Jorgacevski, J., Kreft, M., Zorec, R., Rosa, J.M., Gandia, L., Gutirrez, L.M., Binz, T., Giniatullin, R., Kavalali, E.T. and Davletov, B. Sphingosine facilitates SNARE complex assembly and activates synaptic vesicle exocytosis. Neuron 62 (2009) 683–694.

  33. 33.

    Blood, P. and Voth, G. Direct observation of bin/amphiphysin/rvs (BAR) domain-induced membrane curvature by means of molecular dynamics simulations. Proc. Nat. Acad. Sci. USA 103 (2006) 15068–15072.

  34. 34.

    Kabaso, D., Gongadze, E., Elter, P., van Rienen, U., Gimsa, J., Kralj-Iglič, V. and Iglič, A. Attachment of rod-like (BAR) proteins and membrane shape. Mini Rev. Med. Chem. 11 (2011) 272–282.

  35. 35.

    Lobasso, S., Saponetti, M.S., Polidoro, F., Lopalco, P., Urbanija, J., Kralj-Iglič, V. and Corcelli, A. Archaebacterial lipid membranes as models to study the interaction of 10-N-nonyl acridine orange with phospholipids. Chem. Phys. Lipids. 157 (2009) 12–20.

Download references

Author information



Corresponding author

Correspondence to Doron Kabaso.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kabaso, D., Gongadze, E., Jorgačevski, J. et al. Exploring the binding dynamics of BAR proteins. Cell Mol Biol Lett 16, 398–411 (2011).

Download citation

Key words

  • BAR proteins
  • Binding dynamics
  • Patch clamp
  • Charged lipids
  • Intrinsic shape