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Nano Research

, Volume 11, Issue 2, pp 913–928 | Cite as

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

  • Karin Kornmueller
  • Bernhard Lehofer
  • Gerd Leitinger
  • Heinz Amenitsch
  • Ruth Prassl
Open Access
Research Article

Abstract

Lipids exhibit an extraordinary polymorphism in self-assembled mesophases, with lamellar phases as the most relevant biological representative. To mimic lipid lamellar phases with amphiphilic designer peptides, seven systematically varied short peptides were engineered. Indeed, four peptide candidates (V4D, V4WD, V4WD2, I4WD2) readily self-assembled into lamellae in aqueous solution. Small-angle X-ray scattering (SAXS) patterns revealed ordered lamellar structures with a repeat distance of ∼ 4–5 nm. Transmission electron microscopy (TEM) images confirmed the presence of stacked sheets. Two derivatives (V3D and V4D2) remained as loose aggregates dispersed in solution; one peptide (L4WD2) formed twisted tapes with internal lamellae and an antiparallel β-type monomer alignment. To understand the interaction of peptides with lipids, they were mixed with phosphatidylcholines. Low peptide concentrations (1.1 mM) induced the formation of a heterogeneous mixture of vesicular structures. Large multilamellar vesicles (MLV, d-spacing ∼ 6.3 nm) coexisted with oligo- or unilamellar vesicles (∼ 50 nm in diameter) and bicelle-like structures (∼ 45 nm length, ∼ 18 nm width). High peptide concentrations (11 mM) led to unilamellar vesicles (ULV, diameter ∼ 260–280 nm) with a homogeneous mixing of lipids and peptides. SAXS revealed the temperature-dependent fine structure of these ULVs. At 25 °C the bilayer is in a fully interdigitated state (headgroup-to-headgroup distance dHH ∼ 2.9 nm), whereas at 50 °C this interdigitation opens up (dHH ∼ 3.6 nm). Our results highlight the versatility of self-assembled peptide superstructures. Subtle changes in the amino acid composition are key design elements in creating peptide- or lipidpeptide nanostructures with richness in morphology similar to that of naturally occurring lipids.

Keywords

amphiphilic designer peptides lipids nanostructures lamellae small-angle X-ray scattering (SAXS) transmission electron microscopy (TEM) 

Notes

Acknowledgements

This work has been supported by the Austrian Science Fund (FWF Project No. I 1109-N28 to R. P.). We gratefully acknowledge Elisabeth Pritz for her support and technical guidance with electron microscopy. We thank Hanna Lindermuth and Hans Krebs for technical assistance.

Supplementary material

12274_2017_1702_MOESM1_ESM.pdf (1.4 mb)
Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

References

  1. [1]
    van Meer, G.; de Kroon, A. I. P. M. Lipid map of the mammalian cell. J. Cell Sci. 2011, 124, 5–8.CrossRefGoogle Scholar
  2. [2]
    van Meer, G.; Voelker, D. R.; Feigenson, G. W. Membrane lipids: Where they are and how they behave. Nat. Rev. Mol. Cell Biol. 2008, 9, 112–124.CrossRefGoogle Scholar
  3. [3]
    Tardieu, A.; Luzzati, V.; Reman, F. C. Structure and polymorphism of the hydrocarbon chains of lipids: A study of lecithin-water phases. J. Mol. Biol. 1973, 75, 711–718, IN17–IN19, 719–733.CrossRefGoogle Scholar
  4. [4]
    Luzzati, V.; Husson, F. The structure of the liquid-crystalline phases of lipid-water systems. J. Cell Biol. 1962, 12, 207–219.CrossRefGoogle Scholar
  5. [5]
    Luzzati, V.; Spegt, P. A. Polymorphism of lipids. Nature 1967, 215, 701–704.CrossRefGoogle Scholar
  6. [6]
    Zhao, X. B.; Pan, F.; Xu, H.; Yaseen, M.; Shan, H. H.; Hauser, C. A. E.; Zhang, S. G.; Lu, J. R. Molecular selfassembly and applications of designer peptide amphiphiles. Chem. Soc. Rev. 2010, 39, 3480–3498.CrossRefGoogle Scholar
  7. [7]
    Khoe, U.; Yang, Y. L.; Zhang, S. G. Self-assembly of nanodonut structure from a cone-shaped designer lipid-like peptide surfactant. Langmuir 2009, 25, 4111–4114.CrossRefGoogle Scholar
  8. [8]
    Hamley, I. W. Self-assembly of amphiphilic peptides. Soft Matter 2011, 7, 4122–4138.CrossRefGoogle Scholar
  9. [9]
    Dehsorkhi, A.; Castelletto, V.; Hamley, I. W. Self-assembling amphiphilic peptides. J. Pept. Sci. 2014, 20, 453–467.CrossRefGoogle Scholar
  10. [10]
    Han, S. Y.; Cao, S. S.; Wang, Y. M.; Wang, J. Q.; Xia, D. H.; Xu, H.; Zhao, X. B.; Lu, J. R. Self-assembly of short peptide amphiphiles: The cooperative effect of hydrophobic interaction and hydrogen bonding. Chem.—Eur. J. 2011, 17, 13095–13102.CrossRefGoogle Scholar
  11. [11]
    Kornmueller, K.; Letofsky-Papst, I.; Gradauer, K.; Mikl, C.; Cacho-Nerin, F.; Leypold, M.; Keller, W.; Leitinger, G.; Amenitsch, H.; Prassl, R. Tracking morphologies at the nanoscale: Self-assembly of an amphiphilic designer peptide into a double helix superstructure. Nano Res. 2015, 8, 1822–1833.CrossRefGoogle Scholar
  12. [12]
    Zhao, Y. R.; Deng, L.; Wang, J. Q.; Xu, H.; Lu, J. R. Solvent controlled structural transition of KI4K self-assemblies: From nanotubes to nanofibrils. Langmuir 2015, 31, 12975–12983.CrossRefGoogle Scholar
  13. [13]
    Zhao, Y. R.; Wang, J. Q.; Deng, L.; Zhou, P.; Wang, S. J.; Wang, Y. T.; Xu, H.; Lu, J. R. Tuning the self-assembly of short peptides via sequence variations. Langmuir 2013, 29, 13457–13464.CrossRefGoogle Scholar
  14. [14]
    Cenker, Ç. Ç.; Bomans, P. H. H.; Friedrich, H.; Dedeoglu, B.; Aviyente, V.; Olsson, U.; Sommerdijk, N. A. J. M.; Bucak, S. Peptide nanotube formation: A crystal growth process. Soft Matter 2012, 8, 7463–7470.CrossRefGoogle Scholar
  15. [15]
    Hauser, C. A. E.; Deng, R. S.; Mishra, A.; Loo, Y.; Khoe, U.; Zhuang, F.R.; Cheong, D. W.; Accardo, A.; Sullivan, M. B.; Riekel, C. et al. Natural tri- to hexapeptides self-aßsemble in water to amyloid ß-type fiber aggregates by unexpected a-helical intermediate structures. Proc. Natl. Acad. Sci. USA 2011, 108, 1361–1366.CrossRefGoogle Scholar
  16. [16]
    Yao, Y.; Xue, M.; Chen, J. Z.; Zhang, M. M.; Huang, F. H. An amphiphilic pillar[5]arene: Synthesis, controllable selfassembly in water, and application in calcein release and TNT adsorption. J. Am. Chem. Soc. 2012, 134, 15712–15715.CrossRefGoogle Scholar
  17. [17]
    Yu, G. C.; Ma, Y. J.; Han, C. Y.; Yao, Y.; Tang, G. P.; Mao, Z. W.; Gao, C. Y.; Huang, F. H. A sugar-functionalized amphiphilic pillar[5]arene: Synthesis, self-assembly in water, and application in bacterial cell agglutination. J. Am. Chem. Soc. 2013, 135, 10310–10313.CrossRefGoogle Scholar
  18. [18]
    Zhao, X. J.; Nagai, Y.; Reeves, P. J.; Kiley, P.; Khorana, H. G.; Zhang, S. G. Designer short peptide surfactants stabilize G protein-coupled receptor bovine rhodopsin. Proc. Natl. Acad. Sci. USA 2006, 103, 17707–17712.CrossRefGoogle Scholar
  19. [19]
    Matsumoto, K.; Vaughn, M.; Bruce, B. D.; Koutsopoulos, S.; Zhang, S. G. Designer peptide surfactants stabilize functional photosystem-I membrane complex in aqueous solution for extended time. J. Phys. Chem. B 2009, 113, 75–83.CrossRefGoogle Scholar
  20. [20]
    Ge, B. S.; Yang, F.; Yu, D. Y.; Liu, S.; Xu, H. Designer amphiphilic short peptides enhance thermal stability of isolated photosystem-I. PLoS One 2010, 5, e10233.CrossRefGoogle Scholar
  21. [21]
    Corin, K.; Baaske, P.; Ravel, D. B.; Song, J. Y.; Brown, E.; Wang, X. Q.; Wienken, C. J.; Jerabek-Willemsen, M.; Duhr, S.; Luo, Y.et al. Designer lipid-like peptides: A class of detergents for studying functional olfactory receptors using commercial cell-free systems. PLoS One 2011, 6, e25067.CrossRefGoogle Scholar
  22. [22]
    Wang, X. Q.; Corin, K.; Baaske, P.; Wienken, C. J.; Jerabek-Willemsen, M.; Duhr, S.; Braun, D.; Zhang, S. G. Peptide surfactants for cell-free production of functional G protein-coupled receptors. Proc. Natl. Acad. Sci. USA 2011, 108, 9049–9054.CrossRefGoogle Scholar
  23. [23]
    Koutsopoulos, S.; Kaiser, L.; Eriksson, H. M.; Zhang, S. G. Designer peptide surfactants stabilize diverse functional membrane proteins. Chem. Soc. Rev. 2012, 41, 1721–1728.CrossRefGoogle Scholar
  24. [24]
    Chen, C. X.; Pan, F.; Zhang, S. Z.; Hu, J.; Cao, M. W.; Wang, J.; Xu, H.; Zhao, X. B.; Lu, J. R. Antibacterial activities of short designer peptides: A link between propensity for nanostructuring and capacity for membrane destabilization. Biomacromolecules 2010, 11, 402–411.CrossRefGoogle Scholar
  25. [25]
    Dehsorkhi, A.; Castelletto, V.; Hamley, I. W.; Seitsonen, J.; Ruokolainen, J. Interaction between a cationic surfactantlike peptide and lipid vesicles and its relationship to antimicrobial activity. Langmuir 2013, 29, 14246–14253.CrossRefGoogle Scholar
  26. [26]
    Fatouros, D. G.; Lamprou, D. A.; Urquhart, A. J.; Yannopoulos, S. N.; Vizirianakis, I. S.; Zhang, S. G.; Koutsopoulos, S. Lipid-like self-assembling peptide nanovesicles for drug delivery. ACS Appl. Mater. Interfaces 2014, 6, 8184–8189.CrossRefGoogle Scholar
  27. [27]
    Briuglia, M.-L.; Urquhart, A. J.; Lamprou, D. A. Sustained and controlled release of lipophilic drugs from a selfassembling amphiphilic peptide hydrogel. Int. J. Pharm. 2014, 474, 103–111.CrossRefGoogle Scholar
  28. [28]
    Karavasili, C.; Spanakis, M.; Papagiannopoulou, D.; Vizirianakis, I. S.; Fatouros, D. G.; Koutsopoulos, S. Bioactive selfassembling lipid-like peptides as permeation enhancers for oral drug delivery. J. Pharm. Sci. 2015, 104, 2304–2311.CrossRefGoogle Scholar
  29. [29]
    Wiradharma, N.; Tong, Y. W.; Yang, Y. Y. Self-assembled oligopeptide nanostructures for co-delivery of drug and gene with synergistic therapeutic effect. Biomaterials 2009, 30, 3100–3109.CrossRefGoogle Scholar
  30. [30]
    Ruan, L. P.; Zhang, H. Y.; Luo, H. L.; Liu, J. P.; Tang, F. S.; Shi, Y. K.; Zhao, X. J. Designed amphiphilic peptide forms stable nanoweb, slowly releases encapsulated hydrophobic drug, and accelerates animal hemostasis. Proc. Natl. Acad. Sci. USA 2009, 106, 5105–5110.CrossRefGoogle Scholar
  31. [31]
    Wu, E. C.; Zhang, S. G.; Hauser, C. A. E. Self-assembling peptides as Cell-interactive scaffolds. Adv. Funct. Mater. 2012, 22, 456–468.CrossRefGoogle Scholar
  32. [32]
    Loo, Y.; Zhang, S. G.; Hauser, C. A. E. From short peptides to nanofibers to macromolecular assemblies in biomedicine. Biotechnol. Adv. 2012, 30, 593–603.CrossRefGoogle Scholar
  33. [33]
    Kornmueller, K.; Lehofer, B.; Meindl, C.; Fröhlich, E.; Leitinger, G.; Amenitsch, H.; Prassl, R. Peptides at the interface: Self-assembly of amphiphilic designer peptides and their membrane interaction propensity. Biomacromolecules 2016, 17, 3591–3601.CrossRefGoogle Scholar
  34. [34]
    Wimley, W. C.; White, S. H. Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat. Struct. Biol. 1996, 3, 842–848.CrossRefGoogle Scholar
  35. [35]
    Pepdraw. Peptide Structure [Online]. http://pepdraw.com/ (accessed Mar 17, 2017).Google Scholar
  36. [36]
    Simm, S.; Einloft, J.; Mirus, O.; Schleiff, E. 50 years of amino acid hydrophobicity scales: Revisiting the capacity for peptide classification. Biol. Res. 2016, 49, 31.CrossRefGoogle Scholar
  37. [37]
    Amenitsch, H.; Rappolt, M.; Kriechbaum, M.; Mio, H.; Laggner, P.; Bernstorff, S. First performance assessment of the small-angle X-ray scattering beamline at ELETTRA. J. Synchrotron Radiat. 1998, 5, 506–508.CrossRefGoogle Scholar
  38. [38]
    Hammersley, A. The FIT2D home page [Online]. http:// www.esrf.eu/computing/scientific/FIT2D/(accessed Mar17, 2017).Google Scholar
  39. [39]
    Orthaber, D.; Bergmann, A.; Glatter, O. SAXS experiments on absolute scale with Kratky systems using water as a secondary standard. J. Appl. Crystallogr. 2000, 33, 218–225.CrossRefGoogle Scholar
  40. [40]
    Pabst, G.; Rappolt, M.; Amenitsch, H.; Laggner, P. Structural information from multilamellar liposomes at full hydration: Full q-range fitting with high quality X-ray data. Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Topics 2000, 62, 4000–4009.Google Scholar
  41. [41]
    Pabst, G.; Koschuch, R.; Pozo-Navas, B.; Rappolt, M.; Lohner, K.; Laggner, P. Structural analysis of weakly ordered membrane stacks. J. Appl. Crystallogr. 2003, 36, 1378–1388.CrossRefGoogle Scholar
  42. [42]
    Nagle, J. F.; Tristram-Nagle, S. Structure of lipid bilayers. Biochim. Biophys. Acta 2000, 1469, 159–195.CrossRefGoogle Scholar
  43. [43]
    Yang, P. W.; Lin, T. L.; Hu, Y.; Jeng, U. S. A time-resolved study on the interaction of oppositely charged bicellesimplications on the charged lipid exchange kinetics. Soft Matter 2015, 11, 2237–2242.CrossRefGoogle Scholar
  44. [44]
    Pabst, G.; Danner, S.; Karmakar, S.; Deutsch, G.; Raghunathan, V. A. On the propensity of phosphatidylglycerols to form interdigitated phases. Biophys. J. 2007, 93, 513–525.CrossRefGoogle Scholar
  45. [45]
    Förster, S.; Fischer, S.; Zielske, K.; Schellbach, C.; Sztucki, M.; Lindner, P.; Perlich, J. Calculation of scattering-patterns of ordered nano- and mesoscale materials. Adv. Coll. Int. Sci. 2011, 163, 53–83.CrossRefGoogle Scholar
  46. [46]
    Kyte, J.; Doolittle, R. F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 1982, 157, 105–132.CrossRefGoogle Scholar
  47. [47]
    Yau, W. M.; Wimley, W. C.; Gawrisch, K.; White, S. H. The preference of tryptophan for membrane interfaces. Biochemistry 1998, 37, 14713–14718.CrossRefGoogle Scholar
  48. [48]
    Yang, P.-W.; Lin, T.-L.; Lin, T.-Y.; Yang, C.-H.; Hu, Y.; Jeng, U. S. Packing DNA with disc-shaped bicelles. Soft Matter 2013, 9, 11542–11548.CrossRefGoogle Scholar
  49. [49]
    Sanders, C. R.; Prosser, R. S. Bicelles: A model membrane system for all seasons? Structure 1998, 6, 1227–1234.CrossRefGoogle Scholar
  50. [50]
    Seddon, A. M.; Curnow, P.; Booth, P. J. Membrane proteins, lipids and detergents: Not just a soap opera. Biochim. Biophys. Acta 2004, 1666, 105–117.CrossRefGoogle Scholar
  51. [51]
    Liang, B. Y.; Tamm, L. K. NMR as a tool to investigate the structure, dynamics and function of membrane proteins. Nat. Struct. Mol. Biol. 2016, 23, 468–474.CrossRefGoogle Scholar
  52. [52]
    Matsumori, N.; Murata, M. 3D structures of membraneassociated small molecules as determined in isotropic bicelles. Nat. Prod. Rep. 2010, 27, 1480–1492.CrossRefGoogle Scholar

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© The author(s) 2018

Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Karin Kornmueller
    • 1
  • Bernhard Lehofer
    • 1
  • Gerd Leitinger
    • 2
  • Heinz Amenitsch
    • 3
  • Ruth Prassl
    • 1
  1. 1.Institute of BiophysicsMedical University of Graz, BioTechMed-GrazGrazAustria
  2. 2.Institute of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic TechniquesMedical University of GrazGrazAustria
  3. 3.Institute of Inorganic ChemistryGraz University of TechnologyGrazAustria

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