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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References
Chandler, D. Interfaces and the driving force of hydrophobic assembly. Nature 437, 640–647 (2005)
Meyer, E. E., Rosenberg, K. J. & Israelachvili, J. Recent progress in understanding hydrophobic interactions. Proc. Natl Acad. Sci. USA 103, 15739–15746 (2006)
Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002)
Dyson, H. J., Wright, P. E. & Scheraga, H. A. The role of hydrophobic interactions in initiation and propagation of protein folding. Proc. Natl Acad. Sci. USA 103, 13057–13061 (2006)
Davis, J. G., Gierszal, K. P., Wang, P. & Ben-Amotz, D. Water structural transformation at molecular hydrophobic interfaces. Nature 491, 582–585 (2012)
Huang, D. M. & Chandler, D. Temperature and length scale dependence of hydrophobic effects and their possible implications for protein folding. Proc. Natl Acad. Sci. USA 97, 8324–8327 (2000)
Li, I. T. S. & Walker, G. C. Signature of hydrophobic hydration in a single polymer. Proc. Natl Acad. Sci. USA 108, 16527–16532 (2011)
Acharya, H., Vembanur, S., Jamadagni, S. N. & Garde, S. Mapping hydrophobicity at the nanoscale: applications to heterogeneous surfaces and proteins. Faraday Discuss. 146, 353–365 (2010)
Patel, A. J., Varilly, P. & Chandler, D. Fluctuations of water near extended hydrophobic and hydrophilic surfaces. J. Phys. Chem. B 114, 1632–1637 (2010)
Patel, A. J. et al. Sitting at the edge: how biomolecules use hydrophobicity to tune their interactions and function. J. Phys. Chem. B 116, 2498–2503 (2012)
Giovambattista, N., Debenedetti, P. G. & Rossky, P. J. Hydration behavior under confinement by nanoscale surfaces with patterned hydrophobicity and hydrophilicity. J. Phys. Chem. C 111, 1323–1332 (2007)
Li, L., Fennell, C. J. & Dill, K. A. Field-SEA: a model for computing the solvation free energies of nonpolar, polar, and charged solutes in water. J. Phys. Chem. B 118, 6431–6437 (2014)
Johnson, K. L., Kendall, K. & Roberts, A. D. Surface energy and contact of elastic solids. Proc. R. Soc. Lond. A 324, 301–313 (1971)
Young, T. An essay on the cohesion of fluids. Philos. Trans. R. Soc. Lond. 95, 65–87 (1805)
Acevedo-Vélez, C., Andre, G., Dufrene, Y. F., Gellman, S. H. & Abbott, N. L. Single-molecule force spectroscopy of beta-peptides that display well-defined three-dimensional chemical patterns. J. Am. Chem. Soc. 133, 3981–3988 (2011)
Hwang, S., Shao, Q., Williams, H., Hilty, C. & Gao, Y. Q. Methanol strengthens hydrogen bonds and weakens hydrophobic interactions in proteins - a combined molecular dynamics and NMR study. J. Phys. Chem. B 115, 6653–6660 (2011)
Pomerantz, W. C., Grygiel, T. L. R., Lai, J. R. & Gellman, S. H. Distinctive circular dichroism signature for 14-helix-bundle formation by beta-peptides. Org. Lett. 10, 1799–1802 (2008)
Vezenov, D. V., Zhuk, A. V., Whitesides, G. M. & Lieber, C. M. Chemical force spectroscopy in heterogeneous systems: intermolecular interactions involving epoxy polymer, mixed monolayers, and polar solvents. J. Am. Chem. Soc. 124, 10578–10588 (2002)
Wang, J. L., Li, Z. L., Yoon, R. H. & Eriksson, J. C. Surface forces in thin liquid films of n-alcohols and of water-ethanol mixtures confined between hydrophobic surfaces. J. Colloid Interface Sci. 379, 114–120 (2012)
Raguse, T. L., Lai, J. R. & Gellman, S. H. Environment-independent 14-helix formation in short β-peptides: striking a balance between shape control and functional diversity. J. Am. Chem. Soc. 125, 5592–5593 (2003)
Chakrabartty, A. & Baldwin, R. L. Stability of α-helices. Adv. Protein Chem. 46, 141–176 (1995)
Hinterdorfer, P. & Dufrene, Y. F. Detection and localization of single molecular recognition events using atomic force microscopy. Nature Methods 3, 347–355 (2006)
Godawat, R., Jamadagni, S. N. & Garde, S. Unfolding of hydrophobic polymers in guanidinium chloride solutions. J. Phys. Chem. B 114, 2246–2254 (2010)
Lo Nostro, P. & Ninham, B. W. Hofmeister phenomena: an update on ion specificity in biology. Chem. Rev. 112, 2286–2322 (2012)
Pomerantz, W. C., Cadwell, K. D., Hsu, Y. J., Gellman, S. H. & Abbott, N. L. Sequence dependent behavior of amphiphilic β-peptides on gold surfaces. Chem. Mater. 19, 4436–4441 (2007)
Hiemenz, P. C. & Rajagopalan, R. Principles of Colloid and Surface Chemistry 3rd edn (CRC, 1997)
Vezenov, D. V., Noy, A. & Ashby, P. Chemical force microscopy: probing chemical origin of interfacial forces and adhesion. J. Adhes. Sci. Technol. 19, 313–364 (2005)
Drelich, J., Tormoen, G. W. & Beach, E. R. Determination of solid surface tension from particle-substrate pull-off forces measured with the atomic force microscope. J. Colloid Interface Sci. 280, 484–497 (2004)
Alsteens, D., Dague, E., Rouxhet, P. G., Baulard, A. R. & Dufrene, Y. F. Direct measurement of hydrophobic forces on cell surfaces using AFM. Langmuir 23, 11977–11979 (2007)
Skulason, H. & Frisbie, C. D. Rupture of hydrophobic microcontacts in water: correlation of pull-off force with AFM tip radius. Langmuir 16, 6294–6297 (2000)
Awada, H., Castelein, G. & Brogly, M. Quantitative determination of surface energy using atomic force microscopy: the case of hydrophobic/hydrophobic contact and hydrophilic/hydrophilic contact. Surf. Interface Anal. 37, 755–764 (2005)
Israelachvili, J. N. Intermolecular and Surface Forces 3rd edn (Elsevier, 2011)
Ashby, P. D., Chen, L. & Lieber, C. M. Probing intermolecular forces and potentials with magnetic feedback chemical force microscopy. J. Am. Chem. Soc. 122, 9467–9472 (2000)
Seog, J. et al. Direct measurement of glycosaminoglycan intermolecular interactions via high-resolution force spectroscopy. Macromolecules 35, 5601–5615 (2002)
Tian, C. S. & Shen, Y. R. Structure and charging of hydrophobic material/water interfaces studied by phase-sensitive sum-frequency vibrational spectroscopy. Proc. Natl Acad. Sci. USA 106, 15148–15153 (2009)
Zangi, R. & Engberts, J. B. F. N. Physisorption of hydroxide ions from aqueous solution to a hydrophobic surface. J. Am. Chem. Soc. 127, 2272–2276 (2005)
Vácha, R. et al. The orientation and charge of water at the hydrophobic oil droplet-water interface. J. Am. Chem. Soc. 133, 10204–10210 (2011)
Butt, H. J., Cappella, B. & Kappl, M. Force measurements with the atomic force microscope: technique, interpretation and applications. Surf. Sci. Rep. 59, 1–152 (2005)
Burns, A. R., Houston, J. E., Carpick, R. W. & Michalske, T. A. Molecular level friction as revealed with a novel scanning probe. Langmuir 15, 2922–2930 (1999)
Vezenov, D. V., Noy, A. & Lieber, C. M. The effect of liquid-induced adhesion changes on the interfacial shear strength between self-assembled monolayers. J. Adhes. Sci. Technol. 17, 1385–1401 (2003)
Cheng, R. P., Gellman, S. H. & DeGrado, W. F. β-Peptides: from structure to function. Chem. Rev. 101, 3219–3232 (2001)
Pomerantz, W. C. et al. Lyotropic liquid crystals formed from ACHC-rich beta-peptides. J. Am. Chem. Soc. 133, 13604–13613 (2011)
Harder, P., Grunze, M., Dahint, R., Whitesides, G. M. & Laibinis, P. E. Molecular conformation in oligo(ethylene glycol)-terminated self-assembled monolayers on gold and silver surfaces determines their ability to resist protein adsorption. J. Phys. Chem. B 102, 426–436 (1998)
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).
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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.
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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.
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.
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. c–h, 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).
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.
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.
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.
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.
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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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DOI: https://doi.org/10.1038/nature14018
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