Solvent-mediated Forces Research Articles

How Domain Segregation in Ionic Liquids Stabilizes Nanoparticles and Establishes Long-Range Ordering─A Computational Study.

Due to their physical properties including high thermal stability, very low vapor pressure, and high microwave absorption, ionic liquids have attracted great attention as solvents for the synthesis of nanomaterials, being considered as greener alternatives to traditional solvents. While usual solvents often need additives like surfactants, polymers, or other ligands to avoid nanoparticle coalescence, some ionic liquids can stabilize nanoparticles in dispersion without any additive. In order to quantify how the ionic liquids can affect both the aggregation thermodynamics and kinetics, molecular dynamics simulations were performed to simulate the evolution of concentrated dispersions and to compute the potential of mean force between nanoparticles of both hydrophilic and hydrophobic natures in two imidazolium-based ionic liquids, which differ from each other by the length of the cation alkyl group. Depending on the nature of the nanoparticle, structured layers of the polar and apolar regions of the ionic liquid can be formed close to its surface, and those layers lead to activation barriers for dispersed particles to get in contact. If the alkyl group of the ionic liquid is long enough to lead to domain segregation between the ionic and apolar portions of the solvent, the layered structure around the particle becomes more structured and propagates several nanometers away from its surface. This leads to stronger barriers close to the contact and also multiple barriers at larger distances that result from the unfavorable superposition of solvent layers of opposing nature when the nanoparticles approach each other. Those long-range solvent-mediated forces not only provide kinetic stability to dispersions but also affect their dynamics and lead to a long-range ordering between dispersed particles that can be explored as a template for the synthesis of complex materials.

Interpenetration and Friction of Brush-Coated Surfaces under External Load: Analytical Theory and SCF Calculations

We studied the compression and interpenetration properties of two opposing monodisperse polymer brushes under external load by analytical theory and by a numerical self-consistent field (SCF) approach. Analytical expressions are proposed for the brush density profiles in the interpenetration zone and verified by numerical SCF calculations. We quantify the interpenetration of two opposing brushes by the characteristic penetration length and by two integral parameters: the overlap integral, Γ, representing the number of interbush contacts, and the number of brush monomer units in the foreign half-space, Σ. The interpenetration parameters are studied in two conjugate ensembles as functions of the brush separation and of the external pressure. We propose a theoretical description of the solvent-mediated friction force in the low shearing rate regime on the basis of the Brinkman equation for two compressed brushes sliding against each other. We demonstrate that the total friction force which also includes direct brush–brush friction is expressed in terms of Γ and Σ. The SCF data for the interpenetration parameters Γ and Σ and hence for the total sliding friction force in the pressure ensemble collapse onto universal master curves when rescaled by the factor (N/σ)1/3 as suggested by the theory, where N is the chain length and σ is the surface grafting density. Finally, we define the kinetic friction coefficient as a function of the external pressure and analyze its universal rescaled behavior in the two limits of nondraining and free-draining brushes.

Solvent-mediated forces in protein dielectrophoresis.

DEP is an established method to manipulate micrometer-sized particles, but standard continuum theories predict only negligible effects for nanometer-sized proteins despite contrary experimental evidence. A theoretical description of protein DEP needs to consider details on the molecular scale. Previous work toward this goal addressed the role of orientational polarization of static protein dipole moments for dielectrophoretic effects, which successfully predicts the general magnitude of dielectrophoretic forces on proteins but does not readily explain negative DEP forces observed for proteins in some experiments. However, contributions to the protein chemical potential due to protein-water interactions have not yet been considered in this context. Here, we utilize atomistic molecular dynamics simulations to evaluate polarization-induced changes in the protein solvation free energy, which result in a solvent-mediated contribution to dielectrophoretic forces. We quantify solvent-mediated dielectrophoretic forces for two proteins and a small peptide in water, which follow expectations for protein-water dipole-dipole interactions. The magnitude of solvent-mediated dielectrophoretic forces exceeds predictions of nonmolecular continuum theories, but plays a minor role for the total dielectrophoretic force for the simulated proteins due to dominant contributions from the orientational polarization of their static protein dipoles. However, we extrapolate that solvent-mediated contributions to negative protein DEP forces will become increasingly relevant for multidomain proteins, complexes and aggregates with large protein-water interfaces, as well as for high electric field frequencies, which provides a potential mechanism for corresponding experimental observations of negative proteinDEP.

Impact on mechanical robustness of water droplet due to hydrophilic nanoparticles

The mechanical robustness of droplets is a crucial factor for many applications. In the present work, we reported that adding a small and certain number of hydrophilic nanoparticles can significantly enhance the mechanical robustness of water droplets. Among the various hydrophilic nanoparticles investigated, SiO2 was found to be the most effective one. Experiments and molecular dynamics simulations were used to understand the physics of the phenomenon. It turned out that the microscopic structure at the solid–liquid interface becomes more ordered compared to the pure liquid droplet due to the interaction between nanoparticles and liquid molecules. This ordered structure can strengthen the solvent-mediated forces between nanoparticles, which, in turn, enhances the solid-like performance of the liquid surface and thus the robustness of the droplet.

Solvent-Mediated Forces between Ellipsoidal Nanoparticles Adsorbed at Liquid-Vapor Interfaces.

Classical capillary theory predicts that a non-neutrally wetting ellipsoidal particle adsorbed at a liquid–vapor interface will deform the interface. The deformation gives rise to anisotropic capillary forces of a quadrupolar nature that induce strong directionality in the particle interactions. Here, we investigate the interactions between nanoparticles with characteristic lengths of 1–5 nm. We show that the near-field interactions are dominated by solvent-mediated forces, which arise from the fluid packing between the nanoparticles and direct nanoparticle–nanoparticle interactions. The solvent-mediated forces are two orders of magnitude larger than the estimated capillary force. We find that interacting ellipsoidal nanoparticles adsorbed at the liquid–vapor interface have a larger repulsion in the depletion region than the nanoparticles submerged in a dense bulk phase and argue that this is because of a negative line tension associated with the three-phase line.

Hydrodynamic Stress Tensor in Inhomogeneous Colloidal Suspensions: an Irving-Kirkwood Extension**Supported by the National Natural Science Foundation of China under Grant No. 21503077, the Fundamental Research Fund for the Central Universities of China under Grant No. 2016MS156, and the Research Project from Hebei Education Department under Grant No. QN2018119

Based on statistical mechanics for classical fluids, general expressions for hydrodynamic stress in inhomogeneous colloidal suspension are derived on a molecular level. The result is exactly an extension of the Iving-Kirkwood stress for atom fluids to colloidal suspensions where dynamic correlation emerges. It is found that besides the inter-particle distance, the obtained hydrodynamic stress depends closely on the velocity of the colloidal particles in the suspension, which is responsible for the appearance of the solvent-mediated hydrodynamic force. Compared to Brady’s stresslets for the bulk stress, our results are applicable to inhomogeneous suspension, where the inhomogeneity and anisotropy of the dynamic correlation should be taken into account. In the near-field regime where the packing fraction of colloidal particles is high, our results can reduce to those of Brady. Therefore, our results are applicable to the suspensions with low, moderate, or even high packing fraction of colloidal particles.

Understanding the driving forces for crystal growth by oriented attachment through theory and simulations

Abstract

Systematic Coarse-Grained Lipid Force Fields with Semiexplicit Solvation via Virtual Sites.

Despite the central role of lipids in many biophysical functions, the molecular mechanisms that dictate macroscopic lipid behavior remain elusive to both experimental and computational approaches. As such, there has been much interest in the development of low-resolution, implicit-solvent coarse-grained (CG) models to dynamically simulate biologically relevant spatiotemporal scales with molecular fidelity. However, in the absence of solvent, a key challenge for CG models is to faithfully emulate solvent-mediated forces, which include both hydrophilic and hydrophobic interactions that drive lipid aggregation and self-assembly. In this work, we provide a new methodological framework to incorporate semiexplicit solvent effects through the use of virtual CG particles, which represent structural features of the solvent-lipid interface. To do so, we leverage two systematic coarse-graining approaches, multiscale coarse-graining (MS-CG) and relative entropy minimization (REM), in a hybrid fashion to construct our virtual-site CG (VCG) models. As a proof-of-concept, we focus our efforts on two lipid species, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), which adopt a liquid-disordered and gel phase, respectively, at room temperature. Through our analysis, we also present, to our knowledge, the first direct comparison between the MS-CG and REM methods for a complex biomolecule and highlight each of their strengths and weaknesses. We further demonstrate that VCG models recapitulate the rich biophysics of lipids, which enable self-assembly, morphological diversity, and multiple phases. Our findings suggest that the VCG framework is a powerful approach for investigation into macromolecular biophysics.

Initial Aggregation and Ordering Mechanism of Diphenylalanine from Microsecond All-Atom Molecular Dynamics Simulations

Self-assembled diphenylalanine (FF) nanostructures have recently been demonstrated to be interesting materials for antibacterial and anticancer applications. These applications, among others, seek to take advantage of the high-order and resulting appealing physical properties of FF nanostructures by modifying the peptide in some way to achieve specific functionality. To rationally design modifications to the dipeptide that allow for this behavior, the driving forces of FF self-assembly must be understood. Molecular simulations have been utilized to assess these properties but have yielded conflicting conclusions due to inconsistencies in models chosen as well as the lack of quantitative analyses on the specific driving forces. Here, we present an all-atom explicit solvent molecular dynamics-based study on different length scales of FF aggregation. We utilize a free energy decomposition analysis as well as a dimer cluster analysis to identify the initial aggregation driving force to be FF intermolecular electrostatics, whereas solvent-mediated forces drive crystal growth. These data are consistent with the hypothesis that all hydrophobic dipeptides will have a similar initial aggregation mechanism until a critical aggregate size is reached, at which point crystallization occurs and subsequent crystal growth is dominated by solvent-mediated forces. We demonstrate that this proposed mechanism is testable by infrared spectroscopy focusing on the blueshift of the amide I peak as well as the ordering of the carboxylate peak.

Switching Colloidal Superstructures by Critical Casimir Forces.

Recent breakthroughs in colloidal synthesis promise the bottom-up assembly of superstructures on nano- and micrometer length scales, offering molecular analogues on the colloidal scale. However, a structural control similar to that in supramolecular chemistry remains very challenging. Here, colloidal superstructures are built and controlled using critical Casimir forces on patchy colloidal particles. These solvent-mediated forces offer direct analogues of molecular bonds, allowing patch-to-patch binding with exquisite temperature control of bond strength and stiffness. Particles with two patches are shown to form linear chains undergoing morphological changes with temperature, resembling a polymer collapse under poor-solvent conditions. This reversible temperature switching carries over to particles with higher valency, exhibiting a variety of patch-to-patch bonded structures. Using Monte Carlo simulations, it is shown that the collapse results from the growing interaction range favoring close-packed configurations. These results offer new opportunities for the active control of complex structures at the nano and micrometer scale, paving the way to novel temperature-switchable materials.

Solute particle near a nanopore: influence of size and surface properties on the solvent-mediated forces.

Nanoscopic pores are used in various systems to attract nanoparticles. In general the behaviour is a result of two types of interactions: the material specific affinity and the solvent-mediated influence also called the depletion force. The latter is more universal but also much more complex to understand since it requires modeling both the nanoparticle and the solvent. Here, we employed classical density functional theory to determine the forces acting on a nanoparticle near a nanoscopic pore as a function of its hydrophobicity and its size. A simple capillary model is constructed to predict those depletion forces for various surface properties. For a nanoscopic pore, complexity arises from both the specific geometry and the fact that hydrophobic pores are not necessarily filled with liquid. Taking all of these effects into account and including electrostatic effects, we establish a phase diagram describing the entrance and the rejection of the nanoparticle from the pore.

Solvent-mediated forces in critical fluids.

The effective interaction between two planar walls immersed in a fluid is investigated by use of density functional theory in the supercritical region of the phase diagram. A hard core Yukawa model of fluid is studied with special attention to the critical region. To achieve this goal a formulation of the weighted density approximation coupled with the hierarchical reference theory, able to deal with critical long wavelength fluctuations, is put forward and compared with other approaches. The effective interaction between the walls is seen to change character on lowering the temperature: The strong oscillations induced by layering of the molecules, typical of the depletion mechanism in hard core systems, are gradually smoothed and, close to the critical point, a long range attractive tail emerges leading to a scaling form which agrees with the expectations based on the critical Casimir effect. Strong corrections to scaling are seen to affect the results up to very small reduced temperatures. By use of the Derjaguin approximation, this investigation has natural implications for the aggregation of colloidal particles in critical solvents.

Assessing the Quality of Solvents and Dispersants for Low-Dimensional Materials Using the Corresponding Distances Method.

We demonstrate that the corresponding distances method is an accurate, highly efficient, and simple method to assess the quality of solvents and dispersants for low-dimensional nanomaterials. It provides potential of mean force curves at very high resolution from a single simulation using atomistic models with common simulation software. Applying the corresponding distances method to a pair of (10,10) single-wall carbon nanotubes immersed in bromotrichloromethane, we find that bromotrichloromethane is not a solvent for carbon nanotubes. This assessment is in agreement with experimental results but contradicts predictions from Hansen solubility parameters. We argue that the reason for the false-positive prediction of solubility theory is that it does not capture the structural details of the adsorbed solvent layer, which governs the solvent-mediated forces between the tubes.

Protein-protein interactions at high concentrations. Isothermal titration calorimetry determination of human serum albumin-lysozyme interaction enthalpy at several pH values

Macromolecular crowding affects many processes in the cell, where solvent mediated short and long range protein-protein electrostatic interactions, as well as protein-solvent interactions, occur at high protein concentrations in a complex mix of ionic species. The predominant view of macromolecular crowding considers only hard-sphere repulsions (solely entropic). However, as shown recently in the literature, the longer-range interactions can be stronger than the excluded volume effects. In this work, we quantify these interactions using isothermal titration calorimetry. We determined the interaction enthalpy between two proteins, lysozyme and human serum albumin, at high concentrations, at several pH values and, for one case, at three temperatures. We demonstrate that the long-range electrostatic interactions, attractive or repulsive, due to the charges on the protein surfaces dominate the interaction between them, and that the strength of these solvent-mediated forces can be tuned by changing the pH.

Capillary force lithography for cardiac tissue engineering.

Cardiovascular disease remains the leading cause of death worldwide(1). Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart's extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale(2). Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering(3-5). A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling(2). Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart(6-9). Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)(8) and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function(10-14). Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively(15,16). Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA mold is placed on top. For UV-assisted CFL, the PU is then exposed to UV radiation (λ = 250-400 nm) for curing. For solvent-mediated CFL, the PLGA is embossed using heat (120 °C) and pressure (100 kPa). After curing, the PUA mold is peeled off, leaving behind an ANFS for cell culture. Primary cells, such as neonatal rat ventricular myocytes, as well as human pluripotent stem cell-derived cardiomyocytes, can be maintained on the ANFS(2).

In Situ Structure and Dynamics of DNA Origami Determined Through Molecular Dynamics Simulations

The DNA origami method permits folding of long single-stranded DNA into complex three-dimensional structures with sub-nanometer precision. To ensure that such DNA origami objects behave exactly as designed, their structural, mechanical, and kinetic properties must be characterized at both macroscopic and microscopic scales. Transmission electron microscopy, atomic force microscopy and recently cryo-EM tomography have been used to characterize the properties of DNA origami objects, however their microscopic structures and dynamics have remained unknown. Here, we report the results of all-atom molecular dynamics simulations that characterized the structural and mechanical properties of DNA origami objects in unprecedented microscopic detail. When simulated in an aqueous environment, the structures of DNA origami objects depart from their idealized targets as a result of steric, electrostatic and solvent-mediated forces and approach the realistic and relaxed conformations. Whereas the global structural features of such relaxed conformations conform to the experimentally determined features, local deformations are abundant and vary in magnitude along the structures. For example, the Holliday junctions in the DNA origami structures adopt a left-handed antiparallel conformation, which differs considerably from their conformation in solution. The DNA origami structures undergo considerable temporal fluctuations on both local and global scales. Analysis of such structural fluctuations reveals the local mechanical properties of the DNA origami objects. The lattice type of the structures considerably affects global mechanics properties such as bending rigidity. Our study demonstrates the potential of all-atom molecular dynamics simulations to play a considerable role in future development of the DNA origami field by providing accurate, quantitative assessment of local and global structural and mechanical properties of DNA origami objects.

Solvent cavitation under solvophobic confinement

The stability of liquids under solvophobic confinement can tip in favor of the vapor phase, nucleating a liquid-to-vapor phase transition that induces attractive forces between confining surfaces. In the case of water adjacent to hydrophobic surfaces, experimental and theoretical evidence support confinement-mediated evaporation stabilization of biomolecular and colloidal assemblies. The macroscopic thermodynamic theory of cavitation under confinement establishes the connection between the size of the confining surfaces, interfacial free energies, and bulk solvent pressure with the critical evaporation separation and interfacial forces. While molecular simulations have confirmed the broad theoretical trends, a quantitative comparison based on independent measurements of the interfacial free energies and liquid-vapor coexistence properties has, to the best of our knowledge, not yet been performed. To overcome the challenges of simulating a large number of systems to validate scaling predictions for a three-dimensional fluid, we simulate both the forces and liquid-vapor coexistence properties of a two-dimensional Lennard-Jones fluid confined between solvophobic plates over a range of plate sizes and reservoir pressures. Our simulations quantitatively agree with theoretical predictions for solvent-mediated forces and critical evaporation separations once the length dependence of the solvation free energy of an individual confining plate is taken into account. The effective solid-liquid line tension length dependence results from molecular scale correlations for solvating microscopic plates and asymptotically decays to the macroscopic value for plates longer than 150 solvent diameters. The success of the macroscopic thermodynamic theory at describing two-dimensional liquids suggests application to surfactant monolayers to experimentally confirm confinement-mediated cavitation.

Calculation of Local Water Densities in Biological Systems: A Comparison of Molecular Dynamics Simulations and the 3D-RISM-KH Molecular Theory of Solvation

Water plays a unique role in all living organisms. Not only is it nature's ubiquitous solvent, but it also actively takes part in many cellular processes. In particular, the structure and properties of interfacial water near biomolecules such as proteins are often related to the function of the respective molecule. It can therefore be highly instructive to study the local water density around solutes in cellular systems, particularly when solvent-mediated forces such as the hydrophobic effect are relevant. Computational methods such as molecular dynamics (MD) simulations seem well suited to study these systems at the atomic level. However, due to sampling requirements, it is not clear that MD simulations are, indeed, the method of choice to obtain converged densities at a given level of precision. We here compare the calculation of local water densities with two different methods: MD simulations and the three-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH). In particular, we investigate the convergence of the local water density to assess the required simulation times for different levels of resolution. Moreover, we provide a quantitative comparison of the densities calculated with MD and with 3D-RISM-KH and investigate the effect of the choice of the water model for both methods. Our results show that 3D-RISM-KH yields density distributions that are very similar to those from MD up to a 0.5 Å resolution, but for significantly reduced computational cost. The combined use of MD and 3D-RISM-KH emerges as an auspicious perspective for efficient solvent sampling in dynamical systems.

Ion-specific thermodynamic properties of colloids and proteins

Franz Hofmeister established in 1888 that different salt solutions with the same ionic charges have different efficiencies in precipitating proteins from whole egg white. We will discuss how this can be understood from the modified Poisson–Boltzmann equation that accounts for ion specificity via the ion-surface non-electrostatic potential of mean force (NE-PMF) from molecular dynamics simulations. Using this approach, it is at least in principle possible to capture the important physics of the system due to the inclusion of ion-surface van der Waals forces, short range hydration, image potential and different solvent-mediated forces. The method has been proved to be efficient and suitable for describing phenomena where the water structure close to the interface plays an essential role. As an illustrative example, we demonstrate why the double layer force between two gold electrodes coated with hydrophobic self-assembled monolayers in different electrolytes can be highly ion specific. Important thermodynamic properties related to protein aggregation, essential in biotechnology and pharmaceutical industries, can be obtained from the method shown here.

Distinct conformational properties determined by implicit and explicit representation of protein–solvent interactions. An analytical and computer simulation study

In the protein folding problem, solvent-mediated forces are commonly represented by intra-chain pairwise contact energy. Although this approximation has proven to be useful in several circumstances, it is limited in some other aspects of the problem. Here we show that it is possible to achieve two models to represent the chain-solvent system, one of them with implicit and other with explicit solvent, such that both reproduce the same thermodynamic results. Firstly, lattice models treated by analytical methods, were used to show that the implicit and explicitly representation of solvent effects can be energetically equivalent only if local solvent properties are time and spatially invariant. Following, applying the same reasoning used for the lattice models, two inter-consistent Monte Carlo off-lattice models for implicit and explicit solvent are constructed, being that now in the latter the solvent properties are allowed to fluctuate. Then, it is shown that the chain configurational evolution as well as the globule equilibrium conformation are significantly distinct for implicit and explicit solvent systems. Actually, strongly contrasting with the implicit solvent version, the explicit solvent model predicts: (i) a malleable globule, in agreement with the estimated large protein-volume fluctuations; (ii) thermal conformational stability, resembling the conformational heat resistance of globular proteins, in which radii of gyration are practically insensitive to thermal effects over a relatively wide range of temperatures; and (iii) smaller radii of gyration at higher temperatures, indicating that the chain conformational entropy in the unfolded state is significantly smaller than that estimated from random coil configurations. Finally, we comment on the meaning of these results with respect to the understanding of the folding process.