Interaction of amphipathic peptides mediated by elastic membrane deformations

  • S. A. AkimovEmail author
  • V. V. Aleksandrova
  • T. R. Galimzyanov
  • P. V. Bashkirov
  • O. V. Batishchev


Amphipathic alpha-helical peptides are perspective antimicrobial drugs. These peptides are partially embedded into the membrane to a shallow depth so that the longitudinal axis of the helix is parallel to the plane of the membrane or deviates from it by a small angle. In the framework of theory of elasticity of liquid crystals, adapted to lipid membranes, we calculated the energy of deformations occurring near the peptides partially embedded into the membrane. The energy of deformations is minimal when two peptides are parallel to each other and stay at a distance of about 5 nm. This configuration is stable with respect to small parallel displacements of the peptides and with respect to small variation of the angle between their axes both in the plane of the membrane and in the perpendicular direction. As a result of deformation the average thickness of the membrane decreases. The distribution of the elastic energy density has a maximum in the middle between the peptides. This region is the most likely place for formation of the through pores in the membrane. Since the equilibrium distance between the peptides is relatively large, it is assumed that the originally appearing pore should be purely lipidic.


lipid membrane amphipathic peptide antimicrobial peptide pore elasticity theory 


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  1. 1.
    Henderson J.M., Waring A.J., Separovic F., Lee K.Y.C. 2016. Antimicrobial peptides share a common interaction driven by membrane line tension reduction. Biophys. J. 111, 2176–2189.CrossRefPubMedGoogle Scholar
  2. 2.
    Panteleev P.V., Bolosov I.A., Balandin S.V., Ovchinnikova T.V. 2015. Structure and biological functions of ß-hairpin antimicrobial peptides. Acta Naturae. 7, 37–47.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Shenkarev Z.O., Balandin S.V., Trunov K.I., Paramonov A.S., Sukhanov S.V., Barsukov L.I., Arseniev A.S., Ovchinnikova T.V. 2011. Molecular mechanism of action of ß-hairpin antimicrobial peptide arenicin: oligomeric structure in dodecylphosphocholine micelles and pore formation in planar lipid bilayers. Biochemistry. 50, 6255–6265.CrossRefPubMedGoogle Scholar
  4. 4.
    Fuertes G., Gimenez D., Esteban-Martin S., Sanchez-Munoz O.L., Salgado J. 2011. A lipocentric view of peptide-induced pores. Eur. Biophys. J. 40, 399–415.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Perrin B.S., Fu R., Cotten M.L., Pastor R.W. 2016. Simulations of membrane-disrupting peptides II: AMP piscidin 1 favors surface defects over pores. Biophys. J. 111, 1258–1266.CrossRefPubMedGoogle Scholar
  6. 6.
    Kabelka I., Vacha R. 2015. Optimal conditions for opening of membrane pore by amphiphilic peptides. J. Chem. Phys. 143, 243115.CrossRefPubMedGoogle Scholar
  7. 7.
    Pan J., Tieleman D.P., Nagle J.F., Kucerka N., Tristram-Nagle S. 2009. Alamethicin in lipid bilayers: Combined use of X-ray scattering and MD simulations. Biochim. Biophys. Acta Biomembr. 1788, 1387–1397.CrossRefGoogle Scholar
  8. 8.
    Qian S., Wang W., Yang L., Huang H.W. 2008. Structure of transmembrane pore induced by Bax-derived peptide: Evidence for lipidic pores. Proc. Natl. Acad. Sci. USA. 105, 17379–17383.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    He K., Ludtke S., Heller W., Huang H. 1996. Mechanism of alamethicin insertion into lipid bilayers. Biophys. J. 71, 2669–2679.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lee M.-T., Hung W.-C., Chen F.-Y., Huang H.W. 2005. Many-body effect of antimicrobial peptides: On the correlation between lipid’s spontaneous curvature and pore formation. Biophys. J. 89, 4006–4016.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Schwarz G., Stankowski S., Rizzo V. 1986. Thermodynamic analysis of incorporation and aggregation in a membrane: Application to the pore-forming peptide alamethicin. Biochim. Biophys. Acta. 861, 141–151.CrossRefPubMedGoogle Scholar
  12. 12.
    Karal M.A.S., Alam J.M., Takahashi T., Levadny V., Yamazaki M. 2015. Stretch-activated pore of the antimicrobial peptide, magainin 2. Langmuir. 31, 3391–3401.CrossRefPubMedGoogle Scholar
  13. 13.
    Leveritt J.M., Pino-Angeles A., Lazaridis T. 2015. The structure of a melittin-stabilized pore. Biophys. J. 108, 2424–2426.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Perrin B.S., Pastor R.W. 2016. Simulations of membrane- disrupting peptides I: Alamethicin pore stability and spontaneous insertion. Biophys. J. 111, 1248–1257.CrossRefPubMedGoogle Scholar
  15. 15.
    Zemel A., Ben-Shaul A., May S. 2005. Perturbation of a lipid membrane by amphipathic peptides and its role in pore formation. Eur. Biophys. J. 34, 230–242.CrossRefPubMedGoogle Scholar
  16. 16.
    Fuller N.L., Rand, R.P. 2011. The influence of lysolipids on the spontaneous curvature and bending elasticity of phospholipid membranes. Biophys. J. 81, 243–254.CrossRefGoogle Scholar
  17. 17.
    Leikin S., Kozlov M.M., Fuller N.L., Rand R.P. 1996. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes. Biophys. J. 71, 2623–2632.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Galimzyanov T.R., Molotkovsky R.J., Bozdaganyan M.E., Cohen F.S., Pohl P., Akimov S.A. 2015. Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains. Phys. Rev. Lett. 115, 088101.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Abidor I.G., Arakelyan V.B., Chernomordik L.V., Chizmadzhev Y.A., Pastushenko V.F., Tarasevich M.P. 1979. Electric breakdown of bilayer lipid membranes: I. The main experimental facts and their qualitative discussion. J. Electroanal. Chem. 104, 37–52.Google Scholar
  20. 20.
    Evans E., Heinrich V., Ludwig F., Rawicz W. 2003. Dynamic tension spectroscopy and strength of biomembranes. Biophys. J. 85, 2342–2350.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hamm M., Kozlov, M.M. 2000. Elastic energy of tilt and bending of fluid membranes. Eur. Phys. J. E. 3, 323–335.CrossRefGoogle Scholar
  22. 22.
    Nagle J.F., Wilkinson D.A. 1978. Lecithin bilayers. Density measurement and molecular interactions. Biophys. J. 23, 159–175.PubMedGoogle Scholar
  23. 23.
    Molotkovsky R.J., Akimov S.A. 2009. Calculation of line tension in various models of lipid bilayer pore. Biol. Membrany (Rus.). 26, 149–158.Google Scholar
  24. 24.
    Osipenko D.S., Galimzyanov T.R., Akimov S.A. 2016. Lateral redistribution of transmembrane proteins and liquid-ordered domains in lipid membranes with inhomogeneous curvature. Biochemistry (Moscow) Suppl. Series A: Membr. Cell Biol. 10, 259–268.CrossRefGoogle Scholar
  25. 25.
    Akimov S.A., Frolov V.A., Kuzmin P.I., Zimmerberg J., Chizmadzhev Yu.A., Cohen F.S. 2008. Domain formation in membranes caused by lipid wetting of protein. Phys. Rev. E 77, 051901.CrossRefGoogle Scholar
  26. 26.
    Rawicz W., Olbrich K.C., McIntosh T., Needham D., Evans E. 2000. Effect of chain length and unsaturation on elasticity of lipid bilayers. Biophys. J. 79, 328–339.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Hamm M., Kozlov M.M. 1998. Tilt model of inverted amphiphilic mesophase. Eur. Phys. J. B. 6, 519–528.CrossRefGoogle Scholar
  28. 28.
    Rakowska P.D., Jiang H., Ray S., Pyne A., Lamarre B., Carr M., Judge P.J., Ravi J., Gerling U.I.M., Koksch B., Martyna G.J., Hoogenboom B.W., Watts A., Crain J., Grovenor C.R.M., Ryadnov M.G. 2013. Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers. Proc. Natl. Acad. Sci. USA. 110, 8918–8923.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Li C., Salditt T. 2006. Structure of magainin and alamethicin in model membranes studied by X-ray reflectivity. Biophys. J. 91, 3285–3300.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Chen F.-Y., Lee M.-T., Huang H.W. 2003. Evidence for membrane thinning effect as the mechanism for peptideinduced pore formation. Biophys. J. 84, 3751–3758.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Karal, M.A.S., Yamazaki, M. 2015. Communication: Activation energy of tension-induced pore formation in lipid membranes. J. Chem. Phys. 143, 081103.CrossRefPubMedGoogle Scholar
  32. 32.
    Batishchev O.V., Indenbom A.V. 2008. Alkylated glass partition allows formation of solvent-free lipid bilayer by Montal-Mueller technique. Bioelectrochemistry. 74, 22–25.CrossRefPubMedGoogle Scholar
  33. 33.
    Basanez G., Nechushtan A., Drozhinin O., Chanturiya A., Choe E., Tutt S., Wood K.A., Hsu Y.-T., Zimmerberg J., Youle R.J. 1999. Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations. Proc. Natl. Acad. Sci. USA. 96, 5492–5497.CrossRefPubMedPubMedCentralGoogle Scholar

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© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • S. A. Akimov
    • 1
    • 2
    Email author
  • V. V. Aleksandrova
    • 2
  • T. R. Galimzyanov
    • 1
    • 2
  • P. V. Bashkirov
    • 1
    • 3
  • O. V. Batishchev
    • 1
  1. 1.Frumkin Institute of Physical Chemistry and ElectrochemistryRussian Academy of SciencesMoscowRussia
  2. 2.National University of Science and Technology MISiSMoscowRussia
  3. 3.Federal Research and Clinical Center of Physical-Chemical MedicineMoscowRussia

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