Amish J. Patel

Fluctuations of Water near Extended Hydrophobic and Hydrophilic Surfaces

We use molecular dynamics simulations of the SPC-E model of liquid water to derive probability distributions for water density fluctuations in probe volumes of different shapes and sizes, both in the bulk as well as near hydrophobic and hydrophilic surfaces. Our results are obtained with a biased sampling of coarse-grained densities that is easily combined with molecular dynamics integration algorithms. Our principal result is that the probability for density fluctuations of water near a hydrophobic surface, with or without surface water attractions, is akin to density fluctuations at the water-vapor interface. Specifically, the probability of density depletion near the surface is significantly larger than that in the bulk, and this enhanced probability is responsible for hydrophobic forces of assembly. In contrast, we find that the statistics of water density fluctuations near a model hydrophilic surface are similar to that in the bulk.

Sitting at the Edge: How Biomolecules use Hydrophobicity to Tune Their Interactions and Function

Water near extended hydrophobic surfaces is like that at a liquid-vapor interface, where fluctuations in water density are substantially enhanced compared to those in bulk water. Here we use molecular simulations with specialized sampling techniques to show that water density fluctuations are similarly enhanced, even near hydrophobic surfaces of complex biomolecules, situating them at the edge of a dewetting transition. Consequently, water near these surfaces is sensitive to subtle changes in surface conformation, topology, and chemistry, any of which can tip the balance toward or away from the wet state and thus significantly alter biomolecular interactions and function. Our work also resolves the long-standing puzzle of why some biological surfaces dewet and other seemingly similar surfaces do not.

Extended surfaces modulate hydrophobic interactions of neighboring solutes.

Amish J. Patel, Patrick Varilly, Sumanth N. Jamadagni, Hari Acharya, Shekhar Garde, ∗ and David Chandler ∗ Howard P. Isermann Department of Chemical & Biological Engineering, and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA Department of Chemistry, University of California, Berkeley, CA 94720, USA Abstract Interfaces are a most common motif in complex systems. To understand how the presence of interfaces affect hydrophobic phenomena, we use molecular simulations and theory to study hydration of solutes at interfaces. The solutes range in size from sub-nanometer to a few nanometers. The interfaces are self-assembled monolayers with a range of chemistries, from hydrophilic to hydrophobic. We show that the driving force for assembly in the vicinity of a hydrophobic surface is weaker than that in bulk water, and decreases with increasing temperature, in contrast to that in the bulk. We explain these distinct features in terms of an interplay between interfacial fluctuations and excluded volume effects—the physics encoded in Lum-Chandler-Weeks theory [J. Phys. Chem. B 103 4570–4577 (1999)]. Our results suggest a catalytic role for hydrophobic interfaces in the unfolding of proteins, for example, in the interior of chaperonins and in amyloid formation.Interfaces are a most common motif in complex systems. To understand how the presence of interfaces affects hydrophobic phenomena, we use molecular simulations and theory to study hydration of solutes at interfaces. The solutes range in size from subnanometer to a few nanometers. The interfaces are self-assembled monolayers with a range of chemistries, from hydrophilic to hydrophobic. We show that the driving force for assembly in the vicinity of a hydrophobic surface is weaker than that in bulk water and decreases with increasing temperature, in contrast to that in the bulk. We explain these distinct features in terms of an interplay between interfacial fluctuations and excluded volume effects—the physics encoded in Lum–Chandler–Weeks theory [Lum K, Chandler D, Weeks JD (1999) J Phys Chem B 103:4570–4577]. Our results suggest a catalytic role for hydrophobic interfaces in the unfolding of proteins, for example, in the interior of chaperonins and in amyloid formation.

Molecular explanation for why talc surfaces can be both hydrophilic and hydrophobic.

While individual water molecules adsorb strongly on a talc surface (hydrophilic behavior), a droplet of water beads up on the same surface (hydrophobic behavior). To rationalize this dichotomy, we investigated the influence of the microscopic structure of the surface and the strength of adhesive (surface-water) interactions on surface hydrophobicity. We have shown that at low relative humidity, the competition between adhesion and the favorable entropy of being in the vapor phase determines the surface coverage. However, at saturation, it is the competition between adhesion and cohesion (water-water interactions) that determines the surface hydrophobicity. The adhesive interactions in talc are strong enough to overcome the unfavorable entropy, and water adsorbs strongly on talc surfaces. However, they are too weak to overcome the cohesive interactions, and water thus beads up on talc surfaces. Surprisingly, even talc-like surfaces that are highly adhesive do not fully wet at saturation. Instead, a water droplet forms on top of a strongly adsorbed monolayer of water. Our results imply that the interior of hydrophobic zeolites suspended in water may contain adsorbed water molecules at pressures much lower than the intrusion pressure.

An improved coarse-grained model of solvation and the hydrophobic effect

We present a coarse-grained lattice model of solvation thermodynamics and the hydrophobic effect that implements the ideas of Lum-Chandler-Weeks theory [J. Phys. Chem. B 134, 4570 (1999)] and improves upon previous lattice models based on it. Through comparison with molecular simulation, we show that our model captures the length-scale and curvature dependence of solvation free energies with near-quantitative accuracy and 2-3 orders of magnitude less computational effort, and further, correctly describes the large but rare solvent fluctuations that are involved in dewetting, vapor tube formation, and hydrophobic assembly. Our model is intermediate in detail and complexity between implicit-solvent models and explicit-water simulations.

Unraveling the hydrophobic effect, one molecule at a time

Hydrophobicity operates over many scales, from the demixing of oil and water at the macroscopic scale to the folding of proteins in water at the molecular scale. The physics governing hydrophobicity at the two length scales are, however, fundamentally different (1). The hydration of large solutes is governed by surface tension, which favors lower surface area and causes oil drops to coalesce. The surface tension decreases monotonically with increasing temperature, and so does the driving force for coalescence. In contrast, at the microscopic scale, hydrophobic effects vary nonmonotonically, typically becoming stronger and reaching a maximum before decreasing with increasing temperature (e.g., folded proteins can be denatured both by heating and cooling, which implies a maximum in stability as a function of temperature). Theory and simulations predict that the crossover from the molecular to the macroscopic regime occurs at a length scale of the order of 1 nm (1). Because the relevant length scales in proteins range from subnanometer (for side chains exposed in their unfolded states) to several nanometers (in their folded states), understanding of hydration in the crossover region is important for estimating the hydrophobic driving forces in protein folding. Experimental measurements on hydrophobicity in this region have been elusive until now. In PNAS, Li and Walker (2) use single-molecule force spectroscopy of hydrophobic polymers to provide an experimental window into the crossover region.

Pathways to dewetting in hydrophobic confinement.

Significance Dewetting in hydrophobic confinement plays an important role in diverse phenomena, ranging from protein folding and assembly, to the heterogeneous nucleation of vapor bubbles and superhydrophobicity. Using molecular simulations, we find that dewetting proceeds through the formation of isolated cavities adjacent to one of the confining surfaces. These isolated cavities are stabilized by enhanced water density fluctuations, and their growth is uphill in free energy. Upon growing to a certain size, the isolated cavities transition abruptly into supercritical vapor tubes that span the confined region, and grow spontaneously. Consequently, this nonclassical pathway results in lower free energy barriers than anticipated by macroscopic theory, with important implications for the kinetics of dewetting and hence for water-mediated self-assembly. Liquid water can become metastable with respect to its vapor in hydrophobic confinement. The resulting dewetting transitions are often impeded by large kinetic barriers. According to macroscopic theory, such barriers arise from the free energy required to nucleate a critical vapor tube that spans the region between two hydrophobic surfaces—tubes with smaller radii collapse, whereas larger ones grow to dry the entire confined region. Using extensive molecular simulations of water between two nanoscopic hydrophobic surfaces, in conjunction with advanced sampling techniques, here we show that for intersurface separations that thermodynamically favor dewetting, the barrier to dewetting does not correspond to the formation of a (classical) critical vapor tube. Instead, it corresponds to an abrupt transition from an isolated cavity adjacent to one of the confining surfaces to a gap-spanning vapor tube that is already larger than the critical vapor tube anticipated by macroscopic theory. Correspondingly, the barrier to dewetting is also smaller than the classical expectation. We show that the peculiar nature of water density fluctuations adjacent to extended hydrophobic surfaces—namely, the enhanced likelihood of observing low-density fluctuations relative to Gaussian statistics—facilitates this nonclassical behavior. By stabilizing isolated cavities relative to vapor tubes, enhanced water density fluctuations thus stabilize novel pathways, which circumvent the classical barriers and offer diminished resistance to dewetting. Our results thus suggest a key role for fluctuations in speeding up the kinetics of numerous phenomena ranging from Cassie–Wenzel transitions on superhydrophobic surfaces, to hydrophobically driven biomolecular folding and assembly.

On the Thermodynamics and Kinetics of Hydrophobic Interactions at Interfaces

We have studied how primitive hydrophobic interactions between two or more small nonpolar solutes are affected by the presence of surfaces. We show that the desolvation barriers present in the potential of mean force between the solutes in bulk water are significantly reduced near an extended hydrophobic surface. Correspondingly, the kinetics of hydrophobic contact formation and breakage are faster near a hydrophobic surface than near a hydrophilic surface or in the bulk. We propose that the reduction in the desolvation barrier is a consequence of the fact that water near extended hydrophobic surfaces is akin to that at a liquid-vapor interface and is easily displaced. We support this proposal with three independent observations. First, when small hydrophobic solutes are brought near a hydrophobic surface, they induce local dewetting, thereby facilitating the reduction of desolvation barriers. Second, our results and those of Patel et al. (Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 17678-17683) show that, whereas the association of small solutes in bulk water is driven by entropy, that near hydrophobic surfaces is driven by enthalpy, suggesting that the physics of interface deformation is important. Third, moving water away from its vapor-liquid coexistence, by applying hydrostatic pressure, leads to recovery of bulklike signatures (e.g., the presence of a desolvation barrier and an entropic driving force) in the association of solutes. These observations for simple solutes also translate to end-to-end contact formation in a model peptide with hydrophobic end groups, for which lowering of the desolvation barrier and acceleration of contact formation are observed near a hydrophobic surface. Our results suggest that extended hydrophobic surfaces, such as air-water or hydrocarbon-water surfaces, could serve as excellent platforms for catalyzing hydrophobically driven assembly.

Spontaneous recovery of superhydrophobicity on nanotextured surfaces

Significance Due to its aversion to the hydrophobic surface texture, a water droplet makes minimal contact with, and readily rolls off of, a superhydrophobic surface, conferring it with beneficial properties such as water repellency and self-cleaning. However, the surface texture can readily wet in response to conditions such as elevated pressures, leading to a breakdown of superhydrophobicity that is widely believed to be irreversible. By using specialized molecular simulations to study surfaces with nanoscale texture, here we find that the dewetting of the surface texture is strongly influenced by water density fluctuations. Furthermore, an understanding of the dewetting pathways allows us to design novel surface textures on which fluctuations can facilitate a spontaneous recovery of superhydrophobicity. Rough or textured hydrophobic surfaces are dubbed “superhydrophobic” due to their numerous desirable properties, such as water repellency and interfacial slip. Superhydrophobicity stems from an aversion of water for the hydrophobic surface texture, so that a water droplet in the superhydrophobic “Cassie state” contacts only the tips of the rough surface. However, superhydrophobicity is remarkably fragile and can break down due to the wetting of the surface texture to yield the “Wenzel state” under various conditions, such as elevated pressures or droplet impact. Moreover, due to large energetic barriers that impede the reverse transition (dewetting), this breakdown in superhydrophobicity is widely believed to be irreversible. Using molecular simulations in conjunction with enhanced sampling techniques, here we show that on surfaces with nanoscale texture, water density fluctuations can lead to a reduction in the free energetic barriers to dewetting by circumventing the classical dewetting pathways. In particular, the fluctuation-mediated dewetting pathway involves a number of transitions between distinct dewetted morphologies, with each transition lowering the resistance to dewetting. Importantly, an understanding of the mechanistic pathways to dewetting and their dependence on pressure allows us to augment the surface texture design, so that the barriers to dewetting are eliminated altogether and the Wenzel state becomes unstable at ambient conditions. Such robust surfaces, which defy classical expectations and can spontaneously recover their superhydrophobicity, could have widespread importance, from underwater operation to phase-change heat transfer applications.

Sparse Sampling of Water Density Fluctuations in Interfacial Environments

The free energetics of water density fluctuations near a surface, and the rare low-density fluctuations in particular, serve as reliable indicators of surface hydrophobicity; the easier it is to displace the interfacial waters, the more hydrophobic the underlying surface is. However, characterizing the free energetics of such rare fluctuations requires computationally expensive, non-Boltzmann sampling methods like umbrella sampling. This inherent computational expense associated with umbrella sampling makes it challenging to investigate the role of polarizability or electronic structure effects in influencing interfacial fluctuations. Importantly, it also limits the size of the volume, which can be used to probe interfacial fluctuations. The latter can be particularly important in characterizing the hydrophobicity of large surfaces with molecular-level heterogeneities, such as those presented by proteins. To overcome these challenges, here we present a method for the sparse sampling of water density fluctuations, which is roughly 2 orders of magnitude more efficient than umbrella sampling. We employ thermodynamic integration to estimate the free energy differences between biased ensembles, thereby circumventing the umbrella sampling requirement of overlap between adjacent biased distributions. Further, a judicious choice of the biasing potential allows such free energy differences to be estimated using short simulations, so that the free energetics of water density fluctuations are obtained using only a few, short simulations. Leveraging the efficiency of the method, we characterize water density fluctuations in the entire hydration shell of the protein, ubiquitin, a large volume containing an average of more than 600 waters.