Skip to main content

Advertisement

SpringerLink
Log in

Perturbation of a lipid membrane by amphipathic peptides and its role in pore formation

  • Article
  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

We study the structural and energetic consequences of (α-helical) amphipathic peptide adsorption onto a lipid membrane and the subsequent formation of a transmembrane peptide pore. Initially, each peptide binds to the membrane surface, with the hydrophobic face of its cylinder-like body inserted into the hydrocarbon core. Pore formation results from subsequent peptide crowding, oligomerization, and eventually reorientation along the membrane normal. We have theoretically analyzed three peptide–membrane association states: interfacially-adsorbed monomeric and dimeric peptides, and the multi-peptide transmembrane pore state. Our molecular-level model for the lipid bilayer is based on a combination of detailed chain packing theory and a phenomenological description of the headgroup region. We show that the membrane perturbation free energy depends critically on peptide orientation: in the transmembrane pore state the lipid perturbation energy, per peptide, is smaller than in the adsorbed state. This suggests that the gain in conformational freedom of the lipid chains is a central driving force for pore formation. We also find a weak, lipid-mediated, gain in membrane perturbation free energy upon dimerization of interfacially-adsorbed peptides. Although the results pertain mainly to weakly-charged peptides, they reveal general properties of the interaction of amphipathic peptides with lipid membranes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Bak M, Bywater RP, Hohwy M, Thomsen JK, Adelhorst K, Jakobsen H, Sorensen OW, Nielsen NC (2001) Conformation of alamethicin in oriented phospholipid bilayers determined by (15)N solid-state nuclear magnetic resonance. Biophys J 81:1684–1698

    Google Scholar 

  • Balgavý P, Dubničková M, Kučerka N, Kieslev MA, Yaradaikin S, Uhríková D (2001) Bilayer thickness and lipid interface area in unilamellar extruded 1,2-diacylphosphatidylcholine liposomes: a small-angle neutron scattering study. Biochim Biophys Acta 1512:40–52

    Google Scholar 

  • Bechinger B (1999) The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy. Biochim Biophys Acta 1462:157–183

    Google Scholar 

  • Ben-Shaul A, Gelbart WM (1994) Statistical thermodynamics of amphiphile self-assembly: structure and phase transitions in micellar solutions. In: Gelbart WM, Ben-Shaul A, Roux D (eds) Micelles, membranes, microemulsions and monolayers. Springer, New York, Ch1, pp 359–402

  • Cantor RS (2002) Size distribution of barrel-stave aggregates of membrane peptides: Influence of the bilayer lateral pressure profile. Biophys J 82:2520–2525

    Google Scholar 

  • Chen L, Bassolino D, Stouch T (1997) Transmembrane helix structure, dynamics, and interactions: Multi-nanosecond molecular dynamics simulation. Biophys J 73:3–20

    Google Scholar 

  • Dan N, Safran SA (1998) Effect of lipid characteristics on the structure of transmembrane proteins. Biophys J 75:1410–1414

    Google Scholar 

  • Dempsey CE, Ueno S, Avison MB (2003) Enhanced membrane permeabilization and antibacterial activity of a disulfide-dimerized magainin analogue. Biochemistry 42:402–409

    Article  Google Scholar 

  • Douliez JP, Léonard A, Dufourc EJ (1995) Restatement of order parameters in biomembtanes: calculation of C-C bond order parameters from C–D quadrupolar splittings. Biophys J 68:1727–1739

    Google Scholar 

  • Fattal DR, Ben-Shaul A (1993) A molecular model for lipid protein interaction in membranes: the role of hydrophobic mismatch. Biophys J 65:1795–1809

    Google Scholar 

  • Fattal DR, Andelman D, Ben-Shaul A (1995) The vesicle-micelle transition in mixed lipid-surfactant systems: a molecular model. Langmuir 11:1154–1161

    Google Scholar 

  • Hamm M, Kozlov MM (2000) Elastic energy of tilt and bending of fluid membranes. Eur Phys J B 3:323–335

    Google Scholar 

  • He K, Ludtke SJ, Heller WT, Huang HW (1996) Mechanism of alamethicin insertion into lipid bilayers. Biophys J 71:2669–2679

    Google Scholar 

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

    CAS  Google Scholar 

  • Heller WT, He K, Ludtke SJ, Harroun TA, Huang HW (1997) Effect of changing the size of lipid headgroup on peptide insertion into membranes. Biophys J 73:239–244

    Google Scholar 

  • Hristova K, Wimley WC, Mishra VK, Anantharamiah GM, Segrest JP, White SH (1999) An amphipathic α-helix at the membrane interface: A structural study using a novel X-ray diffraction method. J Mol Biol 290:99–117

    Article  Google Scholar 

  • Hristova K, Dempsey CE, White SH (2001) Structure, location, and lipid perturbations of melittin at the membrane interface. Biophys J 80:801–811

    Google Scholar 

  • Huang HW, Wu Y (1991) Lipid-alamethicin interactions influence alamethicin orientation. Biophys J 60:1079–1087

    Google Scholar 

  • Huang HW, Chen FY, Lee MT (2004) Molecular mechanism of peptide-induced pores in membranes. Phys Rev Lett 92:198304

    Article  Google Scholar 

  • Israelachvili JN (1992) Intermolecular and surface forces, 2nd edn. Academic, New York

  • Kessel A, Ben-Tal N, May S (2001) Interactions of cholesterol with lipid bilayers: The preferred configuration and fluctuations. Biophys J 81:643–658

    Google Scholar 

  • Koenig BW, Ferretti JA, Gawrisch K (1999) Site-specific deuterium order parameters and membrane-bound behavior of a peptide fragment from the intracellular domain of HIV-1 gp41. Biochemistry 38:6327–6334

    Article  Google Scholar 

  • Lin J, Baumgaertner A (2000) Stability of a melittin pore in a lipid bilayer: a molecular dynamics study. Biophys J 78:1714–1724

    Google Scholar 

  • Ludtke SJ, He K, Wu Y, Huang HW (1994) Cooperative membrane insertion of magainin correlated with its cytolytic activity. Biochim Biophys Acta 1190:181–184

    Google Scholar 

  • Ludtke SJ, He K, Huang HW (1995) Membrane thinning caused by magainin 2. Biochemistry 34:16764–16769

    Google Scholar 

  • Ludtke SJ, He K, Heller WT, Harroun TA, Yang L, Huang HW (1996) Membrane pores induced by magainin. Biochemistry 35:13723–13728

    Article  PubMed  Google Scholar 

  • Matsuzaki K, Sugishita K, Fujii N, Miyajima K (1995) Molecular basis of membrane selectivity of an antimicrobial peptide, magainin 2. Biochemistry 34:3423–3429

    Google Scholar 

  • Matsuzaki K, Sugishita K, Ishibe N, Ueha M, Nakata S, Miyajima K, Epand RM (1998) Relationship of membrane curvature to the formation of pores by magainin 2. Biochemistry 37:11856–11863

    Article  Google Scholar 

  • May S (2000) Protein-induced bilayer deformations: The lipid tilt degree of freedom. Eur Biophys J 29:17–28

    Article  Google Scholar 

  • May S (2002) Membrane perturbations induced by integral proteins: role of conformational restrictions of the lipid chains. Langmuir 18:6356–6364

    Google Scholar 

  • May S, Ben-Shaul A (1999) Molecular theory of lipid-protein interaction and the Lα−L II transition. Biophys J 76:751–767

    Google Scholar 

  • May S, Ben-Shaul A (2000) A molecular model for lipid-mediated interaction between proteins in membranes. Phys Chem Chem Phys 2:4494–4502

    Article  Google Scholar 

  • Münster C, Lu J, Schinzel S, Bechinger B, Salditt T (2000) Grazing incidence x-ray diffraction of highly aligned phospholipid membranes containing the antimicrobial peptide magainin 2. Eur Biophys J Biophys Lett 28:683–688

    Google Scholar 

  • Münster C, Spaar A, Bechinger B, Salditt T (2002) Magainin 2 in phospholipid bilayers: peptide orientation and lipid chain ordering studied by x-ray diffraction. Biochim biophys Acta 1562:37–44

    Google Scholar 

  • Oren Z, Shai Y (1998) Mode of action of linear amphipathic alpha-helical antimicrobial peptides. Biopolymers 47:451–463

    Google Scholar 

  • Rapaport D, Shai Y (1991) Interaction of fluorescently labeled pardaxin and its analogues with lipid bilayers. J Biol Chem 266:23769–23775

    Google Scholar 

  • Rapaport D, Shai Y (1992) Aggregation and organization of pardaxin in phospholipid membranes. A fluorescence energy transfer study. J Biol Chem 267:6502–6509

    Google Scholar 

  • Rapaport D, Peled R, Nir S, Shai Y (1996) Reversible surface aggregation in pore formation by paradaxin. Biophys J 70:2502–2512

    Google Scholar 

  • Ren J, Lew S, Wang Z, London E (1999) Control of the transmembrane orientation and interhelical interactions within membranes by hydrophobic helix length. Biochemistry 38:5905–5912

    Article  Google Scholar 

  • Sansom MSP (1993) Alamethicin and related peptaibols-model ion channels. Eur Biophys J 22:105–124

    CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Shepherd CM, Vogel HJ, Tieleman DP (2003) Interactions of the designed antimicrobial peptide MB21 and truncated dermaseptin S3 with lipid bilayers: molecular-dynamics simulations. Biochem J 370:233–243

    Article  Google Scholar 

  • Smith R, Separovic F, Milne TJ, Whittaker A, Bennett FM, Cornell BA, Makriyannis A (1994) Structure and orientation of the pore-forming peptide, melittin, in lipid bilayers. J Mol Biol 241:456–466

    Article  Google Scholar 

  • Takei J, Remenyi A, Dempsey CE (1999) Generalized bilayer perturbation from peptide helix dimerization at membrane surfaces: vesicle lysis induced by disulphide-dimerised melittin analogues. FEBS Lett 442:11–14

    Article  Google Scholar 

  • Yang L, Weiss TM, Lehrer RI, Huang HW (2000) Crystallization of antimicrobial pores in membranes: magainin and protegrin. Biophys J 79:2002–2009

    CAS  PubMed  Google Scholar 

  • Yang L, Harroun TA, Weiss TM, Ding L, Huang HW (2001) Barrel-Stave model or Toroidal model? A case study on melittin pores. Biophys J 81:1475–1485

    PubMed  Google Scholar 

  • Zemel A, Fattal DR, Ben-Shaul A (2003) Energetics and self-assembly of amphipathic peptide pores in lipid membranes. Biophys J 84:2242–2255

    Google Scholar 

  • Zemel A, Ben-Shaul A, May S (2004) Membrane perturbation induced by interfacially adsorbed peptides. Biophys J 86:3607–3619

    Article  Google Scholar 

  • Zuckermann MJ, Heimburg T (2001) Insertion and pore formation driven by adsorption of proteins onto lipid bilayer membrane-water interfaces. Biophys J 81:2458–2472

    Google Scholar 

Download references

Acknowledgments

A.Z. thanks the Yeshaya Horowitz Foundation for a doctoral fellowship. S.M. thanks the Thüringer Ministerium für Wissenschaft, Forschung und Kunst. The financial support of the Israel Science Foundation (grant 227/02) and the United States-Israel Binational Science Foundation (grant 2002-75) is gratefully acknowledged. The Fritz Haber Center is supported by the Minerva Foundation, Munich, Germany.

Author information

Authors and Affiliations

  1. Department of Physical Chemistry and the Fritz Haber Research Center, The Hebrew University, Jerusalem, 91904, Israel

    Assaf Zemel & Avinoam Ben-Shaul

  2. Junior Research Group ”Lipid Membranes”, Friedrich-Schiller-Universität Jena, Neugasse 25, Jena, 07743, Germany

    Sylvio May

Authors
  1. Assaf Zemel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avinoam Ben-Shaul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sylvio May
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Avinoam Ben-Shaul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zemel, A., Ben-Shaul, A. & May, S. Perturbation of a lipid membrane by amphipathic peptides and its role in pore formation. Eur Biophys J 34, 230–242 (2005). https://doi.org/10.1007/s00249-004-0445-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00249-004-0445-9

Keywords

Search

Navigation