Analysis of three-dimensional chromatin packing domains by chromatin scanning transmission electron microscopy (ChromSTEM).

Chromatin organization over multiple length scales plays a critical role in the regulation of transcription. Deciphering the interplay of these processes requires high-resolution, three-dimensional, quantitative imaging of chromatin structure in vitro. Herein, we introduce ChromSTEM, a method that utilizes high-angle annular dark-field imaging and tomography in scanning transmission electron microscopy combined with DNA-specific staining for electron microscopy. We utilized ChromSTEM for an in-depth quantification of 3D chromatin conformation with high spatial resolution and contrast, allowing for characterization of higher-order chromatin structure almost down to the level of the DNA base pair. Employing mass scaling analysis on ChromSTEM mass density tomograms, we observed that chromatin forms spatially well-defined higher-order domains, around 80 nm in radius. Within domains, chromatin exhibits a polymeric fractal-like behavior and a radially decreasing mass-density from the center to the periphery. Unlike other nanoimaging and analysis techniques, we demonstrate that our unique combination of this high-resolution imaging technique with polymer physics-based analysis enables us to (i) investigate the chromatin conformation within packing domains and (ii) quantify statistical descriptors of chromatin structure that are relevant to transcription. We observe that packing domains have heterogeneous morphological properties even within the same cell line, underlying the potential role of statistical chromatin packing in regulating gene expression within eukaryotic nuclei.

Adsorption and isomerization of glyoxal and methylglyoxal at the air/hydroxylated silica surface.

We present results from molecular dynamics simulations coupled with enhanced sampling techniques on the adsorption and isomerization of glyoxal (GL) and methylglyoxal (MG) at the air/hydroxylated silica (α-Quartz) interface. GL and MG are two organic compounds present in the atmosphere as oxidation products of both biogenic and anthropogenic precursors. By adsorption and hydration on liquid droplets or wetted dust particles, they can enable aerosol growth in the atmosphere. Moreover, thanks to the different polar characters of their trans and cis conformers, GL and MG have been suggested as possible molecular switches capable of responding to changes in solvent polarity. Here, we show that the hydroxylated silica surface does not significantly catalyze the trans-to-cis isomerization, but it stabilizes the cis-isomers, indicating a higher interfacial cis/trans relative concentration compared to the gas phase. Moreover, adsorbed GL prefers to lie parallel on the silica surface, while adsorbed MG shows a tilted orientation. In particular, we report the aldehyde group pointing upward (downward) to the gas phase (to the silica surface) in trans-MG (cis-MG). These results will help in the rationalization of upcoming experimental and modeling work on the adsorption of ketonic compounds on dust aerosols, while it clarifies the catalytic role of the solid substrate surface in promoting conformational changes.

Self-assembly of Pseudo-Dipolar Nanoparticles at Low Densities and Strong Coupling.

Nanocolloids having directional interactions are highly relevant for designing new self-assembled materials easy to control. In this article we report stochastic dynamics simulations of finite-size pseudo-dipolar colloids immersed in an implicit dielectric solvent using a realistic continuous description of the quasi-hard Coulombic interaction. We investigate structural and dynamical properties near the low-temperature and highly-diluted limits. This system self-assembles in a rich variety of string-like configurations, depicting three clearly distinguishable regimes with decreasing temperature: fluid, composed by isolated colloids; string-fluid, a gas of short string-like clusters; and string-gel, a percolated network. By structural characterization using radial distribution functions and cluster properties, we calculate the state diagram, verifying the presence of string-fluid regime. Regarding the string-gel regime, we show that the antiparallel alignment of the network chains arises as a novel self-assembly mechanism when the characteristic interaction energy exceeds the thermal energy in two orders of magnitude, ud/kBT ≈ 100. This is associated to relevant structural modifications in the network connectivity and porosity. Furthermore, our results give insights about the dynamically-arrested nature of the string-gel regime, where we show that the slow relaxation takes place in minuscule energy steps that reflect local rearrangements of the network.

Tuning the Stereoselectivity and Solvation Selectivity at Interfacial and Bulk Environments by Changing Solvent Polarity: Isomerization of Glyoxal in Different Solvent Environments.

Conformational isomerism plays a central role in organic synthesis and biological processes; however, effective control of isomerization processes still remains challenging and elusive. Here, we propose a novel paradigm for conformational control of isomerization in the condensed phase, in which the polarity of the solvent determines the relative concentration of conformers at the interfacial and bulk regions. By the use of state-of-the-art molecular dynamics simulations of glyoxal in different solvents, we demonstrate that the isomerization process is dipole driven: the solvent favors conformational changes toward conformers having molecular dipoles that better match its polar character. Thus, the solvent polarity modulates the conformational change, stabilizing and selectively segregating in the bulk vs the interface one conformer with respect to the others. The findings in this paper have broader implications affecting systems involving compounds with conformers of different polarity. This work suggests novel mechanisms for tuning the catalytic activity of surfaces in conformationally controlled (photo)chemical reactions and for designing a new class of molecular switches that are active in different solvent environments.

Effect of Shear History on Rheology of Time-Dependent Colloidal Silica Gels.

This paper presents a rheological study describing the effects of shear on the flow curves of colloidal gels prepared with different concentrations of fumed silica (4%, 5%, 6%, and 7%) and a hydrophobic solvent (Hydrocarbon fuel, JP-8). Viscosity measurements as a function of time were carried out at different shear rates (10, 50, 100, 500, and 1000 s-1), and based on this data, a new structural kinetics model was used to describe the system. Previous work has based the analysis of time dependent fluids on the viscosity of the intact material, i.e., before it is sheared, which is a condition very difficult to achieve when weak gels are tested. The simple action of loading the gel in the rheometer affects its structure and rheology, and the reproducibility of the measurements is thus seriously compromised. Changes in viscosity and viscoelastic properties of the sheared material are indicative of microstructural changes in the gel that need to be accounted for. Therefore, a more realistic method is presented in this work. In addition, microscopical images (Cryo-SEM) were obtained to show how the structure of the gel is affected upon application of shear.

Hydrogen bonding and orientation effects on the accommodation of methylamine at the air-water interface.

Methylamine is an abundant amine compound detected in the atmosphere which can affect the nature of atmospheric aerosol surfaces, changing their chemical and optical properties. Molecular dynamics simulation results show that methylamine accommodation on water is close to unity with the hydrophilic head group solvated in the interfacial environment and the methyl group pointing into the air phase. A detailed analysis of the hydrogen bond network indicates stronger hydrogen bonds between water and the primary amine group at the interface, suggesting that atmospheric trace gases will likely react with the methyl group instead of the solvated amine site. These findings suggest new chemical pathways for methylamine acting on atmospheric aerosols in which the methyl group is the site of orientation specific chemistry involving its conversion into a carbonyl site providing hydrophilic groups for uptake of additional water. This conversion may explain the tendency of aged organic aerosols to form cloud condensation nuclei. At the same time, formation of NH2 radical and formaldehyde is suggested to be a new source for NH2 radicals at aerosol surfaces, other than by reaction of absorbed NH3. The results have general implications for the chemistry of other amphiphilic organics, amines in particular, at the surface of atmospherically relevant aerosols.

Ab initio study of the reaction of ozone with bromide ion.

Surface level ozone destruction in polar environments may be initiated by oxidation of bromide ions by ozone, ultimately leading to Br2 production. Ab initio calculations are used to support the development of atmospheric chemistry models, but errors can occur in study of the bromide-ozone reaction due to inappropriate treatment of the many-electron species and the ionic nature of the reaction. In this work, a high level ab initio study is used to take into account the electronic correlation and the polarization effects. Our results show three possible pathways for the reaction. In particular, we find that this process, though endothermic on the singlet spin state surface, can be energetically feasible on the triplet surface. The triplet surface can be reached through photoexcitation of ozone or by the spin crossing of the potential energy surface. Because this process is known to occur in the dark, it may be that it occurs after intersystem crossing to a triplet surface. This paper also provides a starting point calibration for any future ab initio calculation studies of the bromide-ozone reaction, from the gas to the condensed phase.

Structure and dynamics of [PF6][P(1,2,2,4)] from molecular dynamics simulations.

Diethyl(methyl)(isobutyl)phosphonium hexafluorophosphate, [PF6][P(1,2,2,4)], is an organic ionic plastic crystal with potential uses as a solid electrolyte in storage and light harvesting devices. In this work, we present a molecular dynamics simulation study for this material covering an extended temperature range, from 175 to 500 K. The simulations predict a transition from the crystalline to a semi plastic phase at 197 K, the onset of cation jump-like rotations at 280 K, a third transition at 340 K to a full plastic phase, and melting to 450 K. Overall, the simulations show a good agreement with the experimental findings, providing a wealth of detail in the structural and dynamic properties of the system.

Cooperative dynamic and diffusion behavior above and below the dynamical crossover of supercooled water.

Using extensive molecular dynamics simulations combined with a novel approach to analyze the molecular displacements we analyzed the change in the dynamics above and below the crossover temperature T(x) for supercooled water. Our findings suggest that the crossover from fragile to strong glass former occurring at T(x) is related with a change in the diffusion mechanism evidencing the presence of jump-like diffusion at lower temperatures. Also we observe that fluctuations of the local environments are intimately connected with fluctuations in the size and the amount of cooperative cluster of mobile molecules, and in particular we find a highly cooperative nature of the motion at low temperatures.

The water supercooled regime as described by four common water models.

The temperature scale of simple water models in general does not coincide with the natural one. Therefore, in order to make a meaningful evaluation of different water models, a temperature rescaling is necessary. In this paper, we introduce a rescaling using the melting temperature and the temperature corresponding to the maximum of the heat capacity to evaluate four common water models (TIP4P-Ew, TIP4P-2005, TIP5P-Ew and Six-Sites) in the supercooled regime. Although all the models show the same general qualitative behavior, the TIP5P-Ew appears as the best representation of the supercooled regime when the rescaled temperature is used. We also analyze, using thermodynamic arguments, the critical nucleus size for ice growth. Finally, we speculate on the possible reasons why atomistic models do not usually crystalize while the coarse grained mW model do crystallize.

Molecular dynamics simulation of lysozyme adsorption/desorption on hydrophobic surfaces.

In this work, we present a series of fully atomistic molecular dynamics (MD) simulations to study lysozyme's orientation-dependent adsorption on polyethylene (PE) surface in explicit water. The simulations show that depending on the orientation of the initial approach to the surface the protein may adsorb or bounce from the surface. The protein may completely leave the surface or reorient and approach the surface resulting in adsorption. The success of the trajectory to adsorb on the surface is the result of different competing interactions, including protein-surface interactions and the hydration of the protein and the hydrophobic PE surface. The difference in the hydration of various protein sites affects the protein's orientation-dependent behavior. Side-on orientation is most likely to result in adsorption as the protein-surface exhibits the strongest attraction. However, adsorption can also happen when lysozyme's longest axis is tilted on the surface if the protein-surface interaction is large enough to overcome the energy barrier that results from dehydrating both the protein and the surface. Our study demonstrates the significant role of dehydration process on hydrophobic surface during protein adsorption.

Lysozyme adsorption on polyethylene surfaces: why are long simulations needed?

The adsorption of lysozyme onto a polyethylene (PE) surface in an aqueous environment was investigated via molecular dynamics (MD) simulation. The adsorption can be divided into three processes: diffusion to the surface, dehydration induced by hydrophobic surface-protein interactions, and denaturation. The dehydration process is very long, around 70 ns. Structural deformations start soon after the protein reaches the surface and continue during the whole trajectory. The hydrophobic residues are slowly driven toward the surface, inducing changes in the protein's secondary structure. The protein's secondary structural components near the surface are more disturbed than those farther away from the surface. The lysozyme is adsorbed with its long axis parallel to the surface and displays an anisotropic mobility on the surface that is probably due to the intrinsic structure of the PE surface. Our study demonstrates the need for long-time atomistic simulation in order to gain a complete understanding of the adsorption process.

Anomalies in supercooled NaCl aqueous solutions: a microscopic perspective.

In this work we studied the effect of NaCl on the thermodynamic and dynamic properties of supercooled water, for salt concentrations between 0.19 and 1.33 mol kg(-1), using molecular dynamic simulations for TIP5P∕E water model and ion parameters specially designed to be used in combination with this potential. We studied the isobaric heat capacity (C(p)) temperature dependence and observed a maximum in C(p), occurring at T(m), that moves to lower temperature values with increasing salt concentration. Many characteristic changes were observed at scaled temperature T∕T(m) ∼ 0.96, namely a minimum in the density of the system, a reduction of the slope of the number of hydrogen bonds vs. temperature, and a crossover from Vogel-Tamman-Fulcher to Arrhenius dynamics. Finally, at low temperatures we observed that water dynamics become heterogeneous with an apparently common relationship between the fraction of immobile molecules and T/T(m) for all studied systems.

Temperature dependence of ice critical nucleus size.

We present a molecular dynamics study of ice growth from supercooled water. By performing a series of simulations with different initial conditions, we have quantitative established the relationship existing between the critical nucleus size and the temperature. The results show that ice embryos containing hundreds or thousands of molecules are needed for the system to crystallize macroscopically, even at high degrees of supercooling. Our findings explain the difficulty in observing spontaneous ice nucleation in atomistic simulations and the relative ease with which water droplets can be supercooled under controlled experiments.

Halide affinity for the water-air interface in aqueous solutions of mixtures of sodium salts.

The water-air interface plays a critical role in many physical and chemical processes of the Earth's atmosphere. In particular, heavy halide ions are strongly involved in processes of fundamental importance in determining the prevalence of many atmospheric components through heterogeneous reactions at the water-air interface. In this work, molecular dynamics simulations are used to study the halide enhancements at the water-air interface in the case of mixtures of Cl(-), Br(-), and I(-) ions. The results show a pattern of enhancement directly correlated to the anion polarizability. This effect is explained in terms of the charge distribution across the slab resembling an electrical double layer. As a result, the anions with higher polarizability lower the system's potential energy by enhancing their presence at the interface.

Kinetics of string-gel formation in a system of dipolar colloidal particles.

The formation of string-gels of dipolar colloidal particles is investigated using molecular dynamics simulations. The characteristic gelation time consistently increases as the temperature of the system increases; it also increases as the density of the system increases. This latter result suggests that the gel formation is not a simple nucleation process. In particular, the energy barriers separating the embryonic nuclei from the final phase appear to be lower for the low-density system, suggesting an important entropic contribution.

Structural transitions and dipole moment of water clusters (H2O)(n=4-100).

The properties of water clusters (H(2)O)(n) over a broad range of sizes (n=4-100) were studied by microcanonical parallel tempering Monte Carlo and replica exchange molecular dynamics simulations at temperatures between 20 and 300 K, with special emphasis in the understanding of relation between the structural transitions and dipole behavior. The effect of the water interaction potential was analyzed using six nonpolarizable models, but more extensive calculations were performed using the TIP4P-ice water model. We find that, in general, the dipole moment of the cluster increases significantly as the cluster melts, suggesting that it could be used to discriminate between the solidlike and liquidlike phases. The effect of a moderate electric field on the cluster heat capacity and total dipole moment was found to be negligible.

Hydrophobic-induced Surface Reorganization: Molecular Dynamics Simulations of Water Nanodroplet on Perfluorocarbon Self-Assembled Monolayers.

We carried out molecular dynamics simulations of water droplets on self-assembled monolayers of perfluorocarbon molecules. The interactions between the water droplet and the hydrophobic fluorocarbon surface were studied by systematically changing the molecular surface coverage and the mobility of the tethered head groups of the surface chain molecules. The microscopic contact angles were determined for different fluorocarbon surface densities. The contact angle at a nanometer length scale does not show a large change with the surface density. The structure of the droplets was studied by looking at the water density profiles and water penetration near the hydrophobic surface. At surface densities near close packed coverage of fluorocarbons, the water density shows an oscillating pattern near the boundary with a robust layered structure. As the surface density decreased and more water molecules penetrated into the fluorocarbon surface, the ordering of the water molecules at the boundary became less pronounced and the layered density structure became diffuse. The water droplet is found to induce the interfacial surface molecules to rearrange and form unique topological structures that minimize the unfavorable water-surface contacts. The local density of the fluorocarbon molecules right below the water droplet is measured to be higher than the density outside the droplet. The density difference increases as the overall surface density decreases. Two different surface morphologies emerge from the water-induced surface reorganization over the range of surface coverage explored in the study. For surface densities near closed packed monolayer coverage, the height of the fluorocarbons is maximum at the center of the droplet and minimum at the water-vapor-surface triple junction, generating a convex surface morphology under the droplet. For lower surface densities, on the other hand, the height of the fluorocarbon surface becomes maximal at and right outside the water-vapor-surface contact line and decreases quickly towards the center of the droplet, forming a concave shape of the surface. The interplay between the fluorocarbon packing and the water molecules is found to have profound consequences in many aspects of surface-water interactions, including water depletion and penetration, hydrogen bonding, and surface morphologies.

Temperature dependent electron binding in (H2O)8.

We combine classical molecular dynamics simulations and quantum density functional theory calculations to study the temperature effects on the electron affinity of the water octamer. The atomistic simulations provide a sample of the cluster's conformations as a function of the temperature, on which the density functional calculations are carried on. As the temperature increases, the cluster undergoes its characteristic phase change from a cubic, solidlike structure to a liquidlike state. This phase change is also reflected by an increase on the total dipole moment of the cluster. The quantum calculations indicate that the large dipole moment conformations have a positive electron affinity. Relaxing the high temperature conformations of the cluster anion to its local minimum, the average vertical detachment energy is calculated and shows a clear tendency to increase as the temperature increases. The analysis of the high temperatures conformations reveals that origin of higher values of the vertical detachment energy is not the stability of the negative octamer but the high energy of the corresponding neutral cluster.