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How Surface Wettability Affects the Binding, Folding, and Dynamics of Hydrophobic Polymers at Interfaces Sumanth N. Jamadagni, Rahul Godawat, and Shekhar Garde* The Howard P. Isermann Department of Chemical & Biological Engineering and the Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180 Received April 3, 2009. Revised Manuscript Received April 27, 2009 We present an extensive molecular simulation study of the behavior of a flexible hydrophobic 25-mer polymer at interfaces presenting a range of chemistries from hydrophobic (-CH3) to hydrophilic (-CONH2). We quantify the free energy of adsorption, conformational equilibria, and translational and conformational dynamics of the polymer at these diverse interfaces. Water-mediated interactions drive the polymer to adsorb strongly at a hydrophobic interface and repel it from hydrophilic ones. At hydrophilic surfaces, van der Waals interactions between the polymer and the surface mitigate this water-mediated repulsion, leading to weak adsorption of the polymer. Although the polymer is strongly adsorbed to hydrophobic surfaces, it is also most dynamic there. Translational diffusion and conformational dynamics are faster at hydrophobic surfaces compared to those at hydrophilic ones. In bulk water, the polymer collapses into compact globular shapes, whereas the thermodynamic stability of folded polymers is significantly lowered at hydrophobic surfaces. The polymer spreads into pancake-like 2D conformations at hydrophobic surfaces and gradually beads up into globular shapes as the surface is made more hydrophilic. Interestingly, the binding thermodynamics and dynamics correlate with macroscopic droplet contact angles that characterize the wetting properties of the different interfaces.
I. Introduction Solid-water interfaces are ubiquitous in biological, colloidal, and soft condensed matter systems. Proteins and biomacromolecules, surfactants and polymers, colloids and other small solutes, and impurities are often interfacially active and adsorb to a variety of interfaces.1-5 Unwanted adsorption is a significant problem in a range of applications from separation processes (e.g., membrane fouling6) to marine coatings7-10 to implants.11,12 Alternatively, one may be interested in controlling and engineering binding in a specific manner leading to an alignment of molecules or pattern formation with applications in sensing and detection.13-16 A fundamental molecular-level understanding of binding phenomena requires the consideration of a system that contains at least three components;a surface, a solvent, and a solute. *Author to whom correspondence should be addressed. E-mail: gardes@ rpi.edu, web page:http://www.rpi.edu/∼gardes. (1) Dickinson, E. Colloids Surf., B 1999, 15, 161–176. (2) Eastoe, J.; Dalton, J. S. Adv. Colloid Interface Sci. 2000, 85, 103–144. (3) Binks, B. P. Curr. Opin. Colloid Interface Sci. 2002, 7, 21–41. (4) Netz, R. R.; Andelman, D. Phys. Rep. Rev. Sec. Phys. Lett. 2003, 380, 1–95. (5) Chakraborty, A. K.; Golumbfskie, A. J. Annu. Rev. Phys. Chem. 2000, 52, 537–73. (6) Le-Clech, P.; Chen, V.; Fane, T. A. G. J. Membr. Sci. 2006, 284, 17–53. (7) Dobretsov, S.; Dahms, H. U.; Qian, P. Y. Biofouling 2006, 22, 43–54. (8) Genzer, J.; Efimenko, K. Biofouling 2006, 22, 339–360. (9) Yebra, D. M.; Kiil, S.; Dam-Johansen, K. Prog. Org. Coat. 2004, 50, 75–104. (10) Schmidt, D. L.; Brady, R. F.; Lam, K.; Schmidt, D. C.; Chaudhury, M. K. Langmuir 2004, 20, 2830–2836. (11) Pavithra, D.; Doble, M. Biomed. Mater. 2008, 3. (12) Wisniewski, N.; Reichert, M. Colloids Surf., B 2000, 18, 197–219. (13) Hayden, O.; Lieberzeit, P. A.; Blaas, D.; Dickert, F. L. Adv. Funct. Mater. 2006, 16, 1269–1278. (14) Choi, I.; Kang, S. K.; Lee, J.; Kim, Y.; Yi, J. Biomaterials 2006, 27, 4655– 4660. (15) Mrksich, M.; Dike, L. E.; Tien, J.; Ingber, D. E.; Whitesides, G. M. Exp. Cell Res. 1997, 235, 305–313. (16) Shi, H. Q.; Tsai, W. B.; Garrison, M. D.; Ferrari, S.; Ratner, B. D. Nature 1999, 398, 593–597.
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The thermodynamics of adsorption are then governed by the interplay of intermolecular interactions between them. In aqueous systems, the structural organization of water molecules near a given surface and a solute induces water-mediated interactions between them.17 These water-induced interactions contribute in addition to the direct surface-solute interactions and can be attractive (e.g., hydrophobic) or repulsive depending on the chemistry and the nature of the surface and the solute. In situations where the solute molecule is conformationally flexible, additional important questions arise regarding preferred conformations in the adsorbed state and the dynamics of conformational transitions at the interface. Hydrophobic polymers are examples of such conformationally flexible solutes, and their behavior in aqueous solutions and at interfaces is of interest for several reasons. In bulk water, these polymers collapse into compact globular structures,18 and their folding thermodynamics displays signatures of thermodynamics of protein folding.19 They are also excellent models to study many-body or larger length scale hydrophobic effects.18-21 Recent simulations from our group show that these polymers are interfacially active and adsorb favorably to hydrophobic solidwater or vapor-water interfaces.22 Interestingly, their conformational equilibria and dynamics are different at those two interfaces, indicating the sensitivity of these polymers to the nature of the interface.22 (17) Paulaitis, M. E. Curr. Opin. Colloid Interface Sci. 1997, 2, 315–320. (18) ten Wolde, P. R.; Chandler, D. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 6539–6543. (19) Athawale, M. V.; Goel, G.; Ghosh, T.; Truskett, T. M.; Garde, S. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 733–738. (20) Ghosh, T.; Garcia, A. E.; Garde, S. J. Am. Chem. Soc. 2001, 123, 10997– 11003. (21) Ferguson, A. L.; Debenedetti, P. G.; Panagiotopoulos, A. Z. J. Phys. Chem. B 2009, 113, 6405–6414 (22) Jamadagni, S. N.; Godawat, J. S.; Dordick, R.; Garde, S. J. Phys. Chem. B 2009, 113, 4093–4101.
Published on Web 06/03/2009
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Indeed, the precise nature of the interface adds an important dimension to the adsorption problem. For example, the extent of hydrophobicity of an interface can influence the behavior of vicinal water significantly and in turn can affect the thermodynamic, structural, and dynamic aspects of adsorption. Recent simulations of solid surfaces of self-assembled monolayers presenting a range of headgroup chemistries to water show clear differences in the behavior of water at these interfaces.23 Hydrophobic surfaces enhance density fluctuations and dynamics of the vicinal water, whereas hydrophilic surfaces suppress them. Higher density fluctuations imply greater ease of formation of cavities and of solvation of hard-sphere solutes at hydrophobic interfaces. Correspondingly, small idealized hydrophobic probe solutes will bind to hydrophobic surfaces and will be repelled away from hydrophilic ones. Although binding affinities of small spherical solutes to different surfaces is of fundamental interest, understanding how larger and conformationally flexible molecules with attractive interactions behave in interfacial environments is of direct relevance to the behavior of proteins, surfactants, and polymers at surfaces. How do model hydrophobic polymers respond to interfaces having a range of chemistries from hydrophobic to hydrophilic? To what surfaces do such polymers “stick”, and what is the magnitude of the binding free energy? What conformational changes occur upon adsorption onto different surfaces? How different are the dynamics at the interface, and to what extent are they influenced by the interfacial chemistry? Here, we address these questions through the analysis of extensive molecular dynamics simulations of systems in which a hydrophobic polymer in water is exposed to interfaces presenting a range of chemistries from hydrophobic to hydrophilic. We quantify the binding free energies, characterize conformational preferences, and investigate the dynamics of the polymer at these interfaces. We show that, to a large extent, interface wettability determines the binding thermodynamics as well as the interfacial structure and dynamics of a hydrophobic polymer. Our results represent an important step toward understanding and quantifying adsorption and binding processes in which macromolecules interact with surfaces of varying chemistries.
II. Methods We performed molecular dynamics simulations of polymer binding to different interfaces as well as of polymer foldingunfolding in bulk water and in interfacial environments. Below we describe key details of our molecular systems and of the methods used. A schematic of the simulation setup is shown in Figure 1. Hydrophobic 25-mer Polymer. The hydrophobic polymer has been used previously by Athawale et al.19 (denoted as CG-25 by them). It comprises a linear chain of 25 freely jointed LennardJones monomers [σmm = 0.44 nm and ɛmm = 0.85 kJ/mol] with harmonic bond potentials [Ubond = 1/2kb(l - l0)2, where kb = 60 702 kJ/mol/nm2 and l0 = 0.25 nm]. In the extended state, the polymer is ∼5.1 nm long and roughly represents a coarse-grained version of a freely jointed C50 alkane chain, with each monomer of the polymer representing an ethane-like unit. Self-Assembled Monolayer (SAM). The SAM is constructed out of surfactants with an alkyl (C10) chain that is attached harmonically to a sulfur atom on one end and presents a headgroup on the other end. Sulfur atoms were position restrained to locations consistent with their positions on gold 111 lattice.24 We did (23) Godawat, R.; Jamadagni, S. N.; Garde, S. Submitted for publication. (24) Love, J. C.; Estroff, L. A.; Kriebel, J. K.; Nuzzo, R. G.; Whitesides, G. M. Chem. Rev. 2005, 105, 1103–1169.
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Figure 1. Snapshot of a part of the MD simulation system showing the hydrophobic polymer (gray spacefill), water (red and white wire frame), and surfactant chains (cyan) with a -CH3 headgroup (CH bonds shown with white sticks) forming the SAM attached to sulfur atoms (yellow spheres) at the other end.
not include the gold atoms but attached two alkane chains (one in the positive and another in the negative z direction) to each sulfur atom creating two SAM-water interfaces in the 3D periodic system. The carbon chain was represented by the united atom model for alkanes.25 Six different chemistries of the headgroup (-CH3, -OCH3, -CONHCH3, -CH2CN, -CONH2, and -OH) were simulated. Parameters derived from AMBER Parm-94 all-atom representation26 was used for all headgroups, except for -CH2CN, where OPLS force field parameters27,28 were used. A total of 224 sulfur atoms were included (i.e., 448 surfactant molecules), leading to the creation of a well-packed crystalline solid SAM phase spanning an area of 6.92 7.00 nm2. The SAM phase was thermally annealed to relax the tilt angle and SAM structure. To verify the SAM surface force- fields, we performed water droplet simulations on the surfaces, and the contact angles in such simulations were close to those measured experimentally.29 Water molecules were represented explicitly using the extended simple point charge model (SPC/E).30 The temperature and pressure were maintained using the Berendsen thermostat and barostat,31 respectively, in all simulations. Electrostatic interactions were calculated using the particle mesh Ewald algorithm.32 Parameters for cross interactions were calculated using standard Lorentz-Berthelot mixing rules.33 All simulations were performed using the molecular dynamics package GROMACS,34,35 (25) Mondello, M.; Grest, G. S.; Webb, E. B.; Peczak, P. J. Chem. Phys. 1998, 109, 798–805. (26) Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Gould, I. R.; Merz, K. M.; Ferguson, D. M.; Spellmeyer, D. C.; Fox, T.; Caldwell, J. W.; Kollman, P. A. J. Am. Chem. Soc. 1995, 117, 5179–5197. (27) Price, M. L. P.; Ostrovsky, D.; Jorgensen, W. L. J. Comput. Chem. 2001, 22, 1340–1352. (28) Watkins, E. K.; Jorgensen, W. L. J. Phys. Chem. A 2001, 105, 4118–4125. (29) Shenogina, N.; Godawat, R.; Keblinski, P.; Garde, S. Phys. Rev. Lett. 2009, 102, 156101. (30) Berendsen, H. J. C.; Grigera, J. R.; Straatsma, T. P. J. Phys. Chem. 1987, 91, 6269–6271. (31) Berendsen, H. J. C.; Postma, J. P. M.; Vangunsteren, W. F.; Dinola, A.; Haak, J. R. J. Chem. Phys. 1984, 81, 3684–3690. (32) Essmann, U.; Perera, L.; Berkowitz, M. L.; Darden, T.; Lee, H.; Pedersen, L. G. J. Chem. Phys. 1995, 103, 8577–8593. (33) Allen, M. P.; J, T. D. Computer Simulation of Liquids; Clarendon Press: Oxford, U.K., 1987. (34) Lindahl, E.; Hess, B.; van der Spoel, D. J. Mol. Model. 2001, 7, 306–317. (35) Berendsen, H. J. C.; Vanderspoel, D.; Vandrunen, R. Comput. Phys. Commun. 1995, 91, 43–56.
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Figure 2. PMF for binding of the hydrophobic polymer to surfaces of different hydrophobicities in the absence of solvent, Wvac(z). For clarity, all curves are translated horizontally such that the minimum in the PMF occurs at z = 0.40 nm.
modified to perform umbrella sampling on Rg. The SHAKE algorithm was used to constrain bonds in water molecules. Free-Energy Calculations Using Umbrella Sampling. Because the polymer molecule is conformationally flexible, the problem of monitoring the polymer conformations, especially in interfacial systems, is a multidimensional one. To reduce the complexity, we consider two of the most important reaction coordinates. One is the radius of gyration of the polymer, Rg, which can distinguish between the compact globular states of the polymer and open extended ones. Second is the distance between the center of mass of the polymer and the solid surface, z. Calculation of the 2D potential of mean force of the polymer, W(Rg, z), is itself computationally extremely demanding. However, the PMF for folding-unfolding, W(Rg), is expected to be most significantly altered from that in bulk water only in the vicinity of the surface. Therefore, we performed three sets of PMF calculations: (a) W(Rg, z = ¥) (i.e., W(Rg) in bulk water), (b) W(Rg, z = zint) (i.e., W(Rg) in the immediate vicinity of the interface), and (c) W (Rg = R*g, z) (i.e., W(z), the PMF for bringing the polymer from infinity to a given distance z from the interface), for a fixed Rg value equal to R*g. We selected R*g = 0.55 nm, which corresponds to that for the most stable configuration in bulk water, and placed a harmonic constraint, 1/2k(Rg - R*g)2, on the Rg of the polymer, with k = 7000 kJ/nm2. The first and second sets of simulations provide the conformational free-energy profile in bulk water and at the interface, whereas the last set provides information about the driving force for the polymer to adsorb onto the interface in a globular conformational state.
III. Results and Discussion Thermodynamics of Polymer Binding to Surfaces of Different Hydrophobicities. The hydrophobic 25-mer polymer is flexible and is expected to have different structural preferences in bulk water and at an interface depending on the interfacial chemistry. We characterize how different interfaces affect polymer conformations later in the article. First, we are interested in quantifying how strongly a folded polymer binds to a surface. To this end, we hold the polymer in an ensemble of globular folded states near Rg ≈ 0.55 nm (which are favored in bulk water) using a harmonic potential and calculate the polymer-surface PMF using umbrella sampling (Methods section). Figure 2 shows the polymer-surface PMF profiles in vacuum (i.e., with no water), Wvac(z), for surfaces comprising self-assembled monolayers of surfactants presenting a range of headgroup chemistries from hydrophobic to hydrophilic. All of the PMFs in vacuum show a qualitatively similar profile. As the 13094 DOI: 10.1021/la9011839
Figure 3. PMF for binding of the hydrophobic polymer to surfaces of different hydrophobicities in the presence of water, W (z). All curves are translated horizontally by the same amounts as in Figure 2.
polymer is brought closer to the interface, the PMF becomes increasingly favorable (
