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Modulation of hydrophobic interactions by proximally immobilized ions

Abstract

The structure of water near non-polar molecular fragments or surfaces mediates the hydrophobic interactions that underlie a broad range of interfacial, colloidal and biophysical phenomena1,2,3,4. Substantial progress over the past decade has improved our understanding of hydrophobic interactions in simple model systems1,5,6,7,8,9,10, but most biologically and technologically relevant structures contain non-polar domains in close proximity to polar and charged functional groups. Theories and simulations exploring such nanometre-scale chemical heterogeneity find it can have an important effect8,10,11,12, but the influence of this heterogeneity on hydrophobic interactions has not been tested experimentally. Here we report chemical force microscopy measurements on alkyl-functionalized surfaces that reveal a dramatic change in the surfaces’ hydrophobic interaction strengths on co-immobilization of amine or guanidine groups. Protonation of amine groups doubles the strength of hydrophobic interactions, and guanidinium groups eliminate measurable hydrophobic interactions in all pH ranges investigated. We see these divergent effects of proximally immobilized cations also in single-molecule measurements on conformationally stable β-peptides with non-polar subunits located one nanometre from either amine- or guanidine-bearing subunits. Our results demonstrate the importance of nanometre-scale chemical heterogeneity, with hydrophobicity not an intrinsic property of any given non-polar domain but strongly modulated by functional groups located as far away as one nanometre. The judicious placing of charged groups near hydrophobic domains thus provides a strategy for tuning hydrophobic driving forces to optimize molecular recognition or self-assembly processes.

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Figure 1: Experimental systems used to investigate the effects of immobilized charge on hydrophobic interactions.
Figure 2: Validation of measurement of hydrophobic interaction by addition of methanol.
Figure 3: Influence of immobilized Am or Gdm on hydrophobic interactions at monolayer surfaces.
Figure 4: Influence of lysine and arginine side chains on hydrophobic interactions involving oligopeptides.

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Acknowledgements

This research was supported by the Wisconsin Nanoscale Science and Engineering Center (NSF grant DMR-0832760). Use of facilities supported by the Wisconsin Materials Research Science and Engineering Center is also acknowledged (NSF grant DMR-1121288).

Author information

Authors and Affiliations

Authors

Contributions

C.D.M. and C.A.-V. synthesized, characterized and performed all force measurements involving oligopeptides. C.W. prepared samples and performed all measurements involving monolayers. S.H.G. and N.L.A. were involved in study design and data interpretation, and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Samuel H. Gellman or Nicholas L. Abbott.

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Competing interests

The authors declare no competing financial interests.

Extended data figures and tables

Extended Data Figure 1 Influence of pH and addition of methanol (60 vol%) on adhesive interactions between self-assembled monolayers and alkyl-terminated AFM tips.

a, Adhesion force histograms for C10H21SH monolayers interacting with an alkyl-terminated AFM tip, measured as a function of pH (red, in TEA; black, in 60 vol% methanol). n = 3,002 (number of test events), N = 3 (number of independent samples) (TEA pH 7); n = 3,084, N = 4 (TEA pH 8); n = 1,076, N = 3 (TEA pH 9); n = 1,288, N = 6 (TEA pH 10.5); n = 3,812, N = 4 (60 vol% MeOH pH 7); n = 4,306, N = 8 (60 vol% MeOH pH 8); n = 1,057, N = 4 (60 vol% MeOH pH 9); n = 1,093, N = 6 (60 vol% MeOH pH 10.5). b, Histograms of adhesion forces measured between an alkyl-terminated AFM tip and monolayers formed from AmC11H22SH, reported as a function of pH (red, in TEA; blue, in 60 vol% methanol). In TEA: n = 1,309, N = 5 at pH 7; n = 1,797, N = 4 at pH 8, n = 1,605, N = 4 at pH 9; n = 1,009, N = 4 at pH 10.5. In 60 vol% methanol: n = 1,772, N = 3 at pH 7; n = 1,614, N = 5 at pH 8; n = 1,603, N = 5 at pH 9; n = 1,151, N = 4 at pH 10.5. c, Histograms of adhesion forces measured between an alkyl-terminated AFM tip and monolayers of GdmC11H22SH, measured as a function of pH (red, in TEA; green, in 60 vol% methanol). In TEA: n = 1,693, N = 4 at pH 7; n = 1,164, N = 4 at pH 8; n = 2,002, N = 4 at pH 9; n = 1,249, N = 3 at pH 10.5. In 60 vol% methanol: n = 1,907, N = 4 at pH 7; n = 1,211, N = 4 at pH 8; n = 2,618, N = 5 at pH 9; n = 1,178, N = 3 at pH 10.5. The histograms show data obtained from all pull-off force curves from all samples.

Source data

Extended Data Figure 2 Comparison of adhesive interactions measured between hydrophobic surfaces in pure water and in aqueous TEA.

Histograms of adhesion forces for C10H21SH monolayers interacting with an alkyl-terminated AFM tip under different solution conditions (red, in TEA at pH 7, n = 3,002, N = 3; blue, in water, n = 4,770, N = 6). The histograms show data obtained from all pull-off force curves from all samples.

Source data

Extended Data Figure 3 Characterization of the composition of mixed monolayers.

a, Ellipsometric thicknesses of monolayers used in this study (n = 3, N = 3). b, Ratio of nitrogen to sulphur signal, obtained by X-ray photoelectron spectroscopy (n = 3, N = 3), for mixed monolayers, plotted as a function of the mole fraction of the Am- or Gdm-terminated alkanethiol in the solution from which the mixed monolayers were formed. Values are means and the error bars show the s.d. of three independent samples. ch, Nitrogen (blue) and sulphur (red) signals obtained by X-ray photoelectron spectroscopy for mixed monolayers formed on the surfaces of gold films: GdmC11H22SH–C10H21SH (c), AmC11H22SH–C10H21SH (d), bare gold (e), GdmC11H22SH (f), AmC11H22SH (g) and C10H21SH (h).

Source data

Extended Data Figure 4 Influence of pH and ionic strength on the distance dependence of the interaction of a hydrophobic AFM tip and an Am-terminated monolayer (on approach).

Approach curves for alkyl-terminated AFM tips interacting with AmC11H22SH monolayers, as measured using the indicated aqueous solution conditions.

Source data

Extended Data Figure 5 Influence of pH and addition of methanol (60 vol%) on adhesive interaction between an alkyl-terminated AFM tip and monolayers containing 90% AmC11H22SH–10% C10H21SH.

a, pH dependence of mean adhesion force measured between an alkyl-terminated AFM tip and Am-containing monolayers: 90% AmC11H22SH–10% C10H21SH in either TEA (red triangles: n = 1,344, N = 4 at pH 7; n = 1,326, N = 5 at pH 8; n = 1,480, N = 4 at pH 9; n = 1,730, N = 4 at pH 10.5) or 60 vol% methanol (blue triangles: n = 972, N = 4 at pH 7; n = 1,548, N = 4 at p 8; n = 1,294, N = 4 at pH 9; n = 1,176, N = 4 at pH 10.5). b, Hydrophobic contribution to the mean adhesion forces measured using 90% AmC11H22SH–10% C10H21SH (red triangles), AmC11H22SH (blue triangles) or C10H21SH (black circles) monolayers. Data show mean ± s.e.m.

Source data

Extended Data Figure 6 Non-globally amphiphilic β-peptide.

Linear and helical representations of the non-globally amphiphilic β-peptide isoGA-Lys.

Extended Data Figure 7 Influence of dissolved anions (MOPS versus Cl) on hydrophobic interaction.

a, The chemical structure of MOPS. b, Hydrophobic contribution to the mean adhesion force measured using monolayers of AmC11H22SH–C10H21SH (red crosses, using MOPS–60 vol% methanol; blue crosses, using TEA–60 vol% methanol), AmC11H22SH (red triangles, using MOPS–60 vol% methanol; blue triangles, using TEA–60 vol% methanol) or C10H21SH (red circles, using MOPS–60 vol% methanol; black circles, using TEA–60 vol% methanol). c, Hydrophobic contribution to the mean adhesion force measured using monolayers of GdmC11H22SH–C10H21SH (red crosses, using MOPS–60 vol% methanol; green crosses, using TEA–60 vol% methanol), GdmC11H22SH (red triangles, using MOPS–60 vol% methanol; green triangles, using TEA–60 vol% methanol) or C10H21SH (red circles, using MOPS–60 vol% methanol; black circles, using TEA–60 vol% methanol). On C10H21SH surface: n = 1,702, N = 4 (MOPS pH 7); n = 1,014, N = 4 (MOPS pH 8); n = 1,006, N = 3 (MOPS pH 9); n = 1,008, N = 4 (MOPS pH 10.5); n = 1,002, N = 4 (MOPS–60 vol% MeOH pH 7); n = 1,000, N = 3 (MOPS–60 vol% MeOH pH 8); n = 1,009, N = 3 (MOPS–60 vol% MeOH pH 9); n = 1,001, N = 4 (MOPS–60 vol% MeOH pH 10.5). On AmC11H22SH–C10H21SH surface: n = 1,100, N = 3 (MOPS pH 7); n = 1,201, N = 4 (MOPS pH 8); n = 989, N = 4 (MOPS pH 9); n = 998, N = 4 (MOPS pH 10.5); n = 1,122, N = 4 (MOPS–60 vol% MeOH pH 7); n = 997, N = 3 (MOPS–60 vol% MeOH pH 8); n = 1,126, N = 4 (MOPS–60 vol% MeOH pH 9); n = 1,328, N = 3 (MOPS–60 vol% MeOH pH 10.5). On GdmC11H22SH surface: n = 1,000, N = 3 (MOPS pH 7); n = 1,001, N = 3 (MOPS pH 8); n = 1,002, N = 3 (MOPS pH 9); n = 1,001, N = 3 (MOPS pH 10.5); n = 1,003, N = 3 (MOPS–60 vol% MeOH pH 7); n = 1,000, N = 3 (MOPS–60 vol% MeOH pH 8); n = 1,001, N = 3 (MOPS–60 vol% MeOH pH 9); n = 1,005, N = 3 (MOPS–60 vol% MeOH pH 10.5). On GdmC11H22SH–C10H21SH surface: n = 999, N = 3 (MOPS pH 7); n = 1,001, N = 3 (MOPS pH 8); n = 1,000, N = 3 (MOPS pH 9); n = 999, N = 3 (MOPS pH 10.5); n = 1,002, N = 3 (MOPS–60 vol% MeOH pH 7); n = 999, N = 3 (MOPS–60 vol% MeOH pH 8); n = 1,001, N = 3 (MOPS–60 vol% MeOH pH 9); n = 1,002, N = 3 (MOPS–60 vol% MeOH pH 10.5). On AmC11H22SH surface: n = 1,004, N = 3 (MOPS pH 7); n = 1,002, N = 3 (MOPS pH 8); n = 1,002, N = 3 (MOPS pH 9); n = 1,002, N = 3 (MOPS pH 10.5); n = 1,001, N = 3 (MOPS 60 vol% MeOH pH 7); n = 1,001, N = 3 (MOPS–60 vol% MeOH pH 8); n = 1,001, N = 3 (MOPS–60 vol% MeOH pH 9); n = 1,001, N = 4 (MOPS–60 vol% MeOH pH 10.5). Measurements were conducted as described in Methods. Data show mean ± s.e.m. Lines are drawn to guide the eye.

Source data

Extended Data Figure 8 Characterization of the widths of adhesion force histograms.

The coefficient of variation was calculated from histograms of the adhesion forces measured using the indicated surfaces (red, in TEA at pH 9; blue, in 60 vol% methanol). Measurements were conducted as detailed in Methods.

Source data

Extended Data Table 1 Statistical information for data shown in Fig. 2b related to the influence of methanol
Extended Data Table 2 Statistical information for data shown in Fig. 2b (pH-dependent data) and Figs 3 and 4

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Ma, C., Wang, C., Acevedo-Vélez, C. et al. Modulation of hydrophobic interactions by proximally immobilized ions. Nature 517, 347–350 (2015). https://doi.org/10.1038/nature14018

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