Tuning underwater adhesion with cation–π interactions

Journal name:
Nature Chemistry
Volume:
9,
Pages:
473–479
Year published:
DOI:
doi:10.1038/nchem.2720
Received
Accepted
Published online

Abstract

Cation–π interactions drive the self-assembly and cohesion of many biological molecules, including the adhesion proteins of several marine organisms. Although the origin of cation–π bonds in isolated pairs has been extensively studied, the energetics of cation–π-driven self-assembly in molecular films remains uncharted. Here we use nanoscale force measurements in combination with solid-state NMR spectroscopy to show that the cohesive properties of simple aromatic- and lysine-rich peptides rival those of the strong reversible intermolecular cohesion exhibited by adhesion proteins of marine mussel. In particular, we show that peptides incorporating the amino acid phenylalanine, a functional group that is conspicuously sparing in the sequences of mussel proteins, exhibit reversible adhesion interactions significantly exceeding that of analogous mussel-mimetic peptides. More broadly, we demonstrate that interfacial confinement fundamentally alters the energetics of cation–π-mediated assembly: an insight that should prove relevant for diverse areas, which range from rationalizing biological assembly to engineering peptide-based biomaterials.

At a glance

Figures

  1. Sequences and molecular structures of the peptides studied.
    Figure 1: Sequences and molecular structures of the peptides studied.

    a,b, Each of the four peptides included one of the amino acids illustrated in b, incorporated in the sequence locations marked by a purple ‘X’ in a. The Lys residues are conserved in each peptide sequence and are marked in blue to emphasize the positive charge of Lys at a pH of 2.5.

  2. Schematic of the SFA set-up and illustration of the surface–peptide–surface interface studied.
    Figure 2: Schematic of the SFA set-up and illustration of the surface–peptide–surface interface studied.

    a, SFA experimental set-up. The peptide was solution deposited onto mica surfaces before placing it into the SFA, and all the experiments were performed in a pH 2.5 buffer solution of 100 mM acetic acid and 250 mM KNO3, without additional dissolved peptide. b, When the two surfaces are compressed into hard contact, a multilayer peptide film is confined between the two surfaces. When the surfaces are separated, failure occurs within the peptide film, which means that the measured work of adhesion is proportional to the intermolecular interactions between peptide molecules.

  3. Representative force–distance data measured for peptides between mica surfaces.
    Figure 3: Representative force–distance data measured for peptides between mica surfaces.

    a, Representative force–distance profiles measured when two mica surfaces are brought together in 100 mM acetic acid and 250 mM KNO3. Measurements were also performed under variable solution salinities and are presented in Supplementary Figs 4 and  5. Positive forces are repulsive and negative forces are attractive. The black data were measured in the absence of adsorbed peptide, and each of the coloured curves corresponds to an experiment in which the peptide was adsorbed onto a single mica surface. b, Representative profiles measured when mica surfaces are separated in 100 mM acetic acid and 250 mM KNO3. The black force–distance profile measured in the absence of peptide exhibits repulsive behaviour, which supports that the adhesion measured in the presence of peptide films results from peptide intermolecular cohesion. The average work of adhesion and associated uncertainty quoted on the plot was obtained from at least ten different force–distance profiles for each peptide. Small variations in peptide-film thicknesses were measured between different experiments, and these variations exhibited no dependence on the peptide molecular structure. Importantly, the work of adhesion does not exhibit a systematic dependence on the film thickness, which implies that the cohesion interactions are independent of minor variations in the film thickness.

  4. Solid-state 2D 13C{1H} HETCOR MAS NMR spectrum acquired from bulk Tyr peptide with a 1D 13C{1H} CP MAS NMR spectrum along the top horizontal axis and a single-pulse 1H MAS NMR spectrum along the left vertical axis.
    Figure 4: Solid-state 2D 13C{1H} HETCOR MAS NMR spectrum acquired from bulk Tyr peptide with a 1D 13C{1H} CP MAS NMR spectrum along the top horizontal axis and a single-pulse 1H MAS NMR spectrum along the left vertical axis.

    Red arrows indicate the intensity correlations that result from the close proximities (<1 nm) of the aromatic b–e 1H moieties of the tyrosine residues (purple letters) and alkyl l and m 13C moieties of the lysine side chains (blue letters). The superscript ‘+’ denotes chemical shifts associated with protonated (positive) lysine residues, whereas the superscript ‘neut.’ denotes chemical shifts associated with neutral lysine residues. The intersection of the shaded red bands indicates a correlated intensity that arises from the proximate alkyl j 13C moieties and protonated amide ε+ 1H moieties of lysine residues, which resonate approximately 0.6 ppm to a lower frequency in the 1H dimension compared with a Leu sample measured under otherwise identical conditions (Supplementary Fig. 5). Such a displacement is consistent with ring-current effects that would result from a configuration of the lysine and tyrosine side chains shown schematically in the inset, associated with inter-residue contact through cation–π electron interactions. All the NMR measurements were conducted at 11.74 T under 10 kHz MAS conditions at 0 °C.

  5. Schematic that depicts the proposed mechanism of cation–π binding in aromatic- and Lys-rich peptide films, with many cation–aromatic binding pairs forming in close proximity.
    Figure 5: Schematic that depicts the proposed mechanism of cation–π binding in aromatic- and Lys-rich peptide films, with many cation–aromatic binding pairs forming in close proximity.

    Each cation–π pair is positively charged, and anion complexation is required to avoid strongly repulsive electrostatic interactions. The most favourable configuration for the anions is within the plane of the aromatic rings, as illustrated by the shaded pink areas that surround the aromatic groups. Aromatic hydroxylation reduces the total volume of favourable anion-interaction sites that are in direct molecular contact with the aromatic ring, illustrated by the reduced pink area in the Dopa panel relative to the Phe panel. Aromatic hydroxylation may also provide a second type of anion interaction site that could be important for anions that form strong hydrogen bonds, illustrated by the green area. The potential importance of hydrogen bonding between ions and aromatic substituents awaits future studies. We propose that an increased configurational entropy within the Phe films is the molecular origin of the increased cohesion present in the Phe peptide relative to the Dopa and Tyr peptides.

References

  1. Ma, J. C. & Dougherty, D. A. The cation–π interaction. Chem. Rev. 97, 13031324 (1997).
  2. Gallivan, J. P. & Dougherty, D. A. Cation–π interactions in structural biology. Proc. Natl Acad. Sci. USA 96, 94599464 (1999).
  3. Crowley, P. B. & Golovin, A. Cation–π interactions in protein–protein interfaces. Proteins. 59, 231239 (2005).
  4. Madahevi, A. S. & Sastry, G. N. Cation–π interaction: its role and relevance in chemistry, biology, and material science. Chem. Rev. 113, 21002138 (2013).
  5. Zhong, W. et al. From ab initio quantum mechanics to molecular neurobiology: a cation–π binding site in the nicotinic receptor. Proc. Natl Acad. Sci. USA 95, 1208812093 (1998).
  6. Khademi, S. et al. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 Å. Science. 305, 15871594 (2004).
  7. Meyer, E. A., Castellano, R. K. & Diederich, F. Interactions with aromatic rings in chemical and biological recognition. Angew. Chem. Int. Ed. 42, 12111250 (2003).
  8. Hwang, D. S., Zeng, H., Lu, Q., Israelachvili, J. N. & Waite, J. H. Adhesion mechanism in a DOPA-deficient foot protein from green mussels. Soft Matter 8, 56405648 (2012).
  9. Lu, Q. et al. Nanomechanics of cation–π interactions in aqueous solutions. Angew. Chem. 125, 40364040 (2013).
  10. Kim, S. et al. Cation–π interaction in DOPA-deficient mussel adhesive protein mfp-1. J. Mater. Chem. B 3, 738743 (2015).
  11. Israelachvili, J. N. Intermolecular and Surface Forces Revised 3rd edn (Academic, 2011).
  12. de Gennes, P. G. Soft adhesives. Langmuir 12, 44974500 (1996).
  13. Rose, S. et al. Nanoparticle solutions as adhesives for gels and biological tissues. Nature 505, 382385 (2014).
  14. Sunner, J., Nishizawa, K. & Kebarle, P. Ion–solvent molecule interactions in the gas phase. The potassium ion and benzene. J. Phys. Chem. 85, 18141820 (1981).
  15. Burley, S. K. & Petsko, G. A. Amino–aromatic interactions in proteins. FEBS Lett. 203, 139143 (1986).
  16. Deakyne, C. A. & Meot-Ner, M. Unconventional hydrogen bonds. 2. NH+π complexes of onium ions with olefins and benzene derivatives. J. Am. Chem. Soc. 107, 474479 (1985).
  17. Lee, B. P., Messersmith, P. B., Israelachvili, J. N. & Waite, J. H. Mussel-inspired adhesives and coatings. Annu. Rev. Mater. Res. 41, 99132 (2011).
  18. Wong Po Foo, C. T. S., Lee, J. S., Mulyasasmita, W., Parisi-Amon, A. & Heilshorn, S. C. Two-component protein-engineered physical hydrogels for cell encapsulation. Proc. Natl Acad. Sci. USA 106, 2206722072 (2009).
  19. Norrby, P. & Liljefors, T. Strong decrease of the benzene–ammonium ion interaction upon complexation with a carboxylate anion. J. Am. Chem. Soc. 121, 23032306 (1999).
  20. Bartoli, S. & Roelens, S. Binding of acetylcholine and tetramethylammonium to a cyclophane receptor: anion's contribution to the cation–π interaction. J. Am. Chem. Soc. 124, 83078315 (2002).
  21. Hunter, C. A., Low, C. M. R., Rotger, C., Vinter, J. G. & Cristiano, Z. The role of the counterion in the cation–π interaction. Chem. Commun. 834835 (2003).
  22. Carrazana-García, J. A., Rodríguez-Otero, J. & Cabaleiro-Lago, E. M. A computational study of anion-modulated cation–π interactions. J. Phys. Chem. B 116, 58605871 (2012).
  23. Carrazana-García, J. A., Cabaleiro-Lago, E. M., Campo-Caharrón, A. & Rodríguez-Otero, J. A theoretical study of ternary indole-cation-anion complexes. Org. Biomol. Chem. 12, 91459156 (2014).
  24. Shao, H. & Stewart, R. J. Biomimetic underwater adhesives with environmentally triggered setting mechanisms. Adv. Mater. 22, 729733 (2010).
  25. Kamino, K., Nakano, M. & Kanai, S. Significance of the conformation of building blocks in curing of barnacle underwater adhesive. FEBS J. 279, 17501760 (2012).
  26. Yamamoto, H. Synthesis and adhesive studies of marine polypeptides. J. Chem. Soc. Perkin Trans. 1 613618 (1987).
  27. Yu, M. & Deming, T. J. Synthetic polypeptide mimics of marine adhesives. Macromolecules 31, 47394745 (1998).
  28. Mattson, K. M. et al. A facile synthesis of catechol-functionalized poly(ethylene oxide) block and random copolymers. J. Polymer Sci. A 53, 26852692 (2015).
  29. Lee, H., Dellatore, S. M., Miller, W. M. & Messersmith, P. B. Mussel-inspired surface chemistry for multifunctional coatings. Science 318, 426430 (2007).
  30. Wang, J. et al. Influence of binding-site density in wet bioadhesion. Adv. Mater. 20, 38723876 (2008).
  31. Wei, W. et al. Bridging adhesion of mussel-inspired peptides: role of charge, chain length, and surface type. Langmuir 31, 11051112 (2015).
  32. Maier, G. P., Rapp, M. V., Waite, J. H., Israelachvili, J. N. & Butler, A. Adaptive synergy between catechol and lysine promotes wet adhesion by surface salt displacement. Science. 349, 628632 (2015).
  33. Danner, E. W., Kan, Y., Hammer, M. U., Israelachvili, J. N. & Waite, J. H. Adhesion of mussel foot protein mefp-5 to mica: an underwater superglue. Biochemistry 51, 65116518 (2012).
  34. Luckham, P. F. & Klein, J. Forces between mica surfaces bearing adsorbed polyelectrolyte, poly-L-lysine, in aqueous media. J. Chem. Soc. Faraday Trans. 1 80, 865878 (1984).
  35. Israelachvili, J. N. et al. Recent advances in the surface forces apparatus (SFA) technique. Rep. Prog. Phys. 73, 036601 (2010).
  36. Guo, C. & Holland, G. Investigating lysine adsorption on fumed silica nanoparticles. J. Phys. Chem. C 118, 2579225801 (2014).
  37. De Vita, E. & Frydman, L. Spectral editing in 13C MAS NMR under moderately fast spinning conditions. J. Magn. Reson. 148, 327337 (2001).
  38. Ando, S. et al. Conformational characterization of glycine residues incorporated into some homopolypeptides by solid-state 13C NMR spectroscopy. J. Am. Chem. Soc. 107, 76487652 (1985).
  39. Selection of non-protonated carbon resonances in solid-state nuclear magnetic-resonance. J. Am. Chem. Soc. 101, 58545856 (1979).
  40. Gomes, J. & Mallion, R. Aromaticity and ring currents. Chem. Rev. 101, 13491383 (2001).
  41. Sever, M. J., Weisser, J. T., Monahan, J., Srinivasan, S. & Wilker, J. J. Metal-mediated cross-linking in the generation of a marine mussel adhesive. Angew. Chem. Int. Ed. 43, 448450 (2004).
  42. Holten-Andersen, N. et al. pH-induced metal–ligand cross-links inspired by mussel yield self-healing polymer networks with near-covalent elastic moduli. Proc. Natl Acad. Sci. USA 108, 26512655 (2011).
  43. Yu, M., Hwang, J. & Deming, T. J. Role of L-3-4-dihydroxyphenylalanine in mussel adhesive proteins. J. Am. Chem. Soc. 121, 58255826 (1999).
  44. Lee, H., Scherer, N. F. & Messersmith, P. B. Single-molecule mechanics of mussel adhesion. Proc. Natl Acad. Sci. USA 103, 1299913003 (2006).
  45. Martinez Rodriguez, N. R., Das, S., Kaufman, Y., Israelachvili, J. N. & Waite, J. H. Interfacial pH during mussel adhesive plaque formation. Biofouling 31, 221227 (2015).
  46. Liaqat, F. et al. High-performance TiO2 nanoparticle/DOPA polymer composites. Macromol. Rapid Commun. 36, 11291137 (2015).
  47. Guardingo, M. et al. Bioinspired catechol-terminated self-assembled monolayers with enhanced adhesion properties. Small 10, 15941602 (2014).
  48. Hediger, S., Meier, B. H., Kurur, N. D., Bodenhausen, G. & Ernst, R. R. NMR cross polarization by adiabatic passage through the Hartmann–Hahn condition (APHH). Chem. Phys. Lett. 223, 283288 (1994).
  49. Elena, B., de Paëpe, G. & Emsley, L. Direct spectral optimisation of proton–proton homonuclear dipolar decoupling in solid-state NMR. Chem. Phys. Lett. 398, 532538 (2004).
  50. Marion, D. & Wüthrich, K. Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of 1H–1H spin-spin coupling constants in proteins. Biochem. Biophys. Res. Commun. 113, 967974 (1983).
  51. Fung, B. M., Khitrin, A. K. & Ermolaev, K. An improved broadband decoupling sequence for liquid crystals and solids. J. Magn. Reson. 142, 97101 (2000).
  52. Hayashi, S. & Hayamizu, K. Chemical shift standards in high-resolution solid-state NMR (1) 13C, 29Si, and 1H nuclei. Bull. Chem. Soc. Jpn 64, 685687 (1991).

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Author information

Affiliations

  1. Materials Department, University of California, Santa Barbara, California 93106, USA

    • Matthew A. Gebbie,
    • Thomas R. Cristiani &
    • Jacob N. Israelachvili
  2. Materials Research Laboratory, University of California, Santa Barbara, California 93106, USA

    • Matthew A. Gebbie,
    • Wei Wei,
    • Alex M. Schrader,
    • J. Herbert Waite &
    • Jacob N. Israelachvili
  3. Department of Molecular, Cell and Developmental Biology, University of California, Santa Barbara, California 93106, USA

    • Alex M. Schrader &
    • J. Herbert Waite
  4. Department of Chemical Engineering, University of California, Santa Barbara, California 93106, USA

    • Howard A. Dobbs,
    • Matthew Idso,
    • Bradley F. Chmelka &
    • Jacob N. Israelachvili

Contributions

M.A.G. and W.W. contributed equally to this work. M.A.G., W.W., J.H.W. and J.N.I. conceived the research. M.A.G., A.M.S. and T.R.C. performed and analysed the force–distance measurements, W.W. synthesized and purified the peptides, M.A.G., H.A.D. and M.I. performed the NMR measurements, H.A.D., M.I. and B.F.C. analysed the NMR results, M.A.G. wrote the paper. All of the authors interpreted the data, discussed the results and commented on the manuscript.

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