Ionic Atmosphere Research Articles

Influence of a Counterion on the Ion Atmosphere of an Anion: A Molecular Dynamics Study of LiX and CsX (X = F(-), Cl(-), I(-)) in Methanol.

We report molecular dynamics (MD) simulations to explore the influence of a counterion on the structure and dynamics of cationic and anionic solvation shells for various ions in methanol at 298 K. We show that the variation in ionic size of either the cation or the anion in an ion pair influences the solvation structure of the other ion as well as the diffusivity in an electrolyte solution of methanol. The extent of ionic association between the cation and its counteranion of different ionic sizes has been investigated by analyzing the radial distribution functions (RDFs) and the orientation of methanol molecules in the first solvation shell (FSS) of ions. It is shown that the methanol in the FSS of the anion as well the cation exhibit quite different radial and orientational structures as compared to methanol which lie in the FSS of either the anion or the cation but not both. We find that the coordination number (CN) of F(-), Cl(-), and I(-) ions decreases with increasing size of the anion which is contrary to the trend reported for the anions in H2O. The mean residence time (MRT) of methanol molecules in the FSS of ions has been calculated using the stable states picture (SSP) approach. It is seen that the ion-counterion interaction has a considerable influence on the MRT of methanol molecules in the FSS of ions. We also discuss the stability order of the ion-counterion using the potentials of mean force (PMFs) for ion pairs with ions of different sizes. The PMF plots reveal that the Li(+)-F(-) pair (small-small) is highly stable and the Li(+)-I(-) pair is least stable (small-large) in electrolyte solutions.

High ionic strength depresses muscle contractility by decreasing both force per cross-bridge and the number of strongly attached cross-bridges.

An increase in ionic strength (IS) lowers Ca(2+) activated tension in muscle fibres, however, its molecular mechanism is not well understood. In this study, we used single rabbit psoas fibres to perform sinusoidal analyses. During Ca(2+) activation, the effects of ligands (ATP, Pi, and ADP) at IS ranging 150-300 mM were studied on three rate constants to characterize elementary steps of the cross-bridge cycle. The IS effects were studied because a change in IS modifies the inter- and intra-molecular interactions, hence they may shed light on the molecular mechanisms of force generation. Both the ATP binding affinity (K1) and the ADP binding affinity (K 0) increased to 2-3x, and the Pi binding affinity (K5) decreased to 1/2, when IS was raised from 150 to 300 mM. The effect on ATP/ADP can be explained by stereospecific and hydrophobic interaction, and the effect on Pi can be explained by the electrostatic interaction with myosin. The increase in IS increased cross-bridge detachment steps (k2 and k-4), indicating that electrostatic repulsion promotes these steps. However, IS did not affect attachment steps (k-2 and k4). Consequently, the equilibrium constant of the detachment step (K2) increased by ~100%, and the force generation step (K4) decreased by ~30%. These effects together diminished the number of force-generating cross-bridges by 11%. Force/cross-bridge (T56) decreased by 26%, which correlates well with a decrease in the Debye length that limits the ionic atmosphere where ionic interactions take place. We conclude that the major effect of IS is a decrease in force/cross-bridge, but a decrease in the number of force generating cross-bridge also takes place. The stiffness during rigor induction did not change with IS, demonstrating that in-series compliance is not much affected by IS.

High-resolution mobility analysis of charge-reduced electrosprayed protein ions.

Many mobility studies (IMS) of electrospray ions with charge states z reduced to unity have shown a singular ability to analyze large protein complexes and viruses, though with wide mobility peaks (fwhm ∼ 20%). Here we confirm that this limitation arises primarily when early charge reduction precedes drop evaporation (suppressing secondary atomization by the usual sequence of many Coulomb explosions). By drying before neutralizing, we achieve a protein fwhm of ∼3.7%. A positively biased electrospraying capillary is coaxial with a cylindrical charge-reduction (CR) chamber coated with radioactive Ni-63 (10 mCi) that fills the CR chamber with a bipolar ionic atmosphere. A screen interposed between the spraying capillary and the CR chamber limits penetration of the neutralizing anions into the electrospray (ES) chamber, precluding destabilization of the ES tip, even when brought very close to the grid to enhance ion transmission. As ES cations cross the grid, driven by their own space charge, they recombine with CR ions reducing their charge state as well as space charge dispersion. The setup is tested with the protein ovalbumin (MW ∼ 44.3 kDa) and its clusters up to the tetramer, by analyzing the charge-reduced ions with a differential mobility analyzer (DMA). At gas sample flow rates of ∼1 L/min, the dominant peaks are singly charged (z = 1). They are widened by clustering of involatile solution impurities, depending on spray quality and solution cleanness, with fwhm as small as 3.7% achieved in desalted and acidified solutions. When using sharp nanospray capillaries, the grid may be removed, resulting in ∼2-fold increased ion transmission. In the absence of the grid, however, spray stability and quality are often compromised, even with capillary tip diameters as small as 30 μm.

Mode coupling theory analysis of electrolyte solutions: Time dependent diffusion, intermediate scattering function, and ion solvation dynamics.

A self-consistent mode coupling theory (MCT) with microscopic inputs of equilibrium pair correlation functions is developed to analyze electrolyte dynamics. We apply the theory to calculate concentration dependence of (i) time dependent ion diffusion, (ii) intermediate scattering function of the constituent ions, and (iii) ion solvation dynamics in electrolyte solution. Brownian dynamics with implicit water molecules and molecular dynamics method with explicit water are used to check the theoretical predictions. The time dependence of ionic self-diffusion coefficient and the corresponding intermediate scattering function evaluated from our MCT approach show quantitative agreement with early experimental and present Brownian dynamic simulation results. With increasing concentration, the dispersion of electrolyte friction is found to occur at increasingly higher frequency, due to the faster relaxation of the ion atmosphere. The wave number dependence of intermediate scattering function, F(k, t), exhibits markedly different relaxation dynamics at different length scales. At small wave numbers, we find the emergence of a step-like relaxation, indicating the presence of both fast and slow time scales in the system. Such behavior allows an intriguing analogy with temperature dependent relaxation dynamics of supercooled liquids. We find that solvation dynamics of a tagged ion exhibits a power law decay at long times-the decay can also be fitted to a stretched exponential form. The emergence of the power law in solvation dynamics has been tested by carrying out long Brownian dynamics simulations with varying ionic concentrations. The solvation time correlation and ion-ion intermediate scattering function indeed exhibit highly interesting, non-trivial dynamical behavior at intermediate to longer times that require further experimental and theoretical studies.

Polyamino acid display on cell surfaces enhances salt and alcohol tolerance of Escherichia coli.

Microbes employ cell membranes for reducing exogenous stresses. Polyamino acid display on microbial cell surfaces and their effects on microbial chemical stress tolerance were examined. Growth analysis revealed that displays of polyarginine, polyaspartate and polytryptophan substantially enhanced tolerance of Escherichia coli to NaCl. A titration assay indicated that polyarginine and polyaspartate altered cell surface charges, implying tolerance enhancement via ion atmosphere and/or ionic bond network formations for electrostatic ion repulsion. The enhancement by polytryptophan may have arisen from surface hydrophobicity increase for hydrophobic ion exclusion, because of a strong correlation between hydrophobic characters of amino acids and their effects on tolerance enhancement. The display also enhanced tolerance to other salts and/or alcohols in E. coli and to NaCl in Saccharomyces cerevisiae. Thus polyamino acid display has the potential as an approach for conferring chemical stress tolerance on various microbes.

CHARMM Drude Polarizable MD Simulations Reproduce Solution X-Ray Diffraction Patterns for B-DNA Sequences and Predict Differential Impact of the Li+, Na+, K+ and Rb+ Ions on DNA Conformational Properties

Recently we have presented the first generation CHARMM Drude polarizable force field for DNA, which is capable of reproducing the main conformational features of DNA in solution, such as A-to-B equilibrium and transitions between BI and BII substates. Our current efforts are directed towards further model improvement, by achieving a proper balance of the interactions among surrounding mobile ions, water and DNA. Compared to the additive (non-polarizable) models, explicit treatment of the electronic polarizability in the Drude model leads to a markedly improved description of the interplay between the ionic atmosphere and DNA conformational behavior. In particular, the Drude model is shown to more accurately reproduce counterion condensation theory predictions of DNA charge neutralization by condensed ions, as well as the experimental data on the competitive binding of Li+, Na+, K+ and Rb+ ions to DNA. The most intriguing results is that the model predicts a differential impact of these seemingly similar monovalent cations on DNA conformational properties - a phenomenon not observed in the state-of-the-art CHARMM36 and AMBER atomistic additive models. In addition, the Drude model reproduces the solution X-ray diffraction patterns for a number of B form DNA sequences at a level of accuracy similar to, or exceeding that of the above mentioned additive models. The obtained results indicate that CHARMM Drude polarizable MD simulations provide a more realistic model of the physical forces involved in the interactions of DNA with its ionic environment, offering the potential to yield new insights into salt-mediated biological processes involving DNA, such as protein-DNA recognition and chromatin folding.

Multiscale methods for computational RNA enzymology.

RNA catalysis is of fundamental importance to biology and yet remains ill-understood due to its complex nature. The multidimensional "problem space" of RNA catalysis includes both local and global conformational rearrangements, changes in the ion atmosphere around nucleic acids and metal ion binding, dependence on potentially correlated protonation states of key residues, and bond breaking/forming in the chemical steps of the reaction. The goal of this chapter is to summarize and apply multiscale modeling methods in an effort to target the different parts of the RNA catalysis problem space while also addressing the limitations and pitfalls of these methods. Classical molecular dynamics simulations, reference interaction site model calculations, constant pH molecular dynamics (CpHMD) simulations, Hamiltonian replica exchange molecular dynamics, and quantum mechanical/molecular mechanical simulations will be discussed in the context of the study of RNA backbone cleavage transesterification. This reaction is catalyzed by both RNA and protein enzymes, and here we examine the different mechanistic strategies taken by the hepatitis delta virus ribozyme and RNase A.

Polymorphic crystal structures of an all-AT DNA dodecamer.

In this work, we explore the influence of different solvents and ions on the crystallization behavior of an all-AT dodecamer d(AATAAATTTATT)2 In all cases, the oligonucleotides are found as continuous columns of stacked duplexes. The spatial organization of such columns is variable; consequently we have obtained seven different crystal forms. The duplexes can be made to crystallize in either parallel or crossed columns. Such versatility in the formation of a variety of crystal forms is characteristic for this sequence. It had not been previously reported for any other sequence. In all cases, the oligonucleotide duplexes have been found to crystallize in the B form. The crystallization conditions determine the organization of the crystal, although no clear local interactions have been detected. Mg(2+) and Ni(2+) can be used in order to obtain compact crossed structures. DNA-DNA interactions in the crystals of our all-AT duplexes present crossovers which are different from those previously reported for mixed sequence oligonucleotides. Our results demonstrate that changes in the ionic atmosphere and the crystallization solvent have a strong influence on the DNA-DNA interactions. Similar ionic changes will certainly influence the biological activity of DNA. Modulation of the crystal structure by ions should also be explored in DNA crystal engineering. Liquid crystals with a peculiar macroscopic shape have also been observed.

Bimodal dielectric relaxation of electrolyte solutions in weakly polar solvents.

The dielectric relaxation spectra of dilute electrolyte solutions in solvents of small dielectric constants are investigated both theoretically and experimentally. The theoretical calculation in our previous work [T. Yamaguchi, T. Matsuoka, and S. Koda, J. Chem. Phys. 135, 164511 (2011)] is reanalyzed, and it is shown that the dielectric relaxation spectra are composed of three components, namely, the relaxation of ionic atmosphere, the reorientational relaxation of ion pairs, and the collision between ions. The relaxation frequency of the slowest one increases with increasing the concentration, and the slower two relaxations, those of ionic atmosphere and ion pairs, merge into one at the concentration where the Debye length is comparable to the size of ions. Experimentally, the dielectric relaxation spectra of some electrolytes in two solvents, tetrahydrofuran and tetraglyme, are determined at frequencies from 300 kHz to 200 MHz, and the presence of the slower two relaxations was confirmed. The concentration dependence of the relaxation frequency is also in harmony with the theoretical calculation. The relationship between the dielectric relaxation spectra and the concentration dependence of the ionic conductivity is discussed.

Excluded volume and ion-ion correlation effects on the ionic atmosphere around B-DNA: theory, simulations, and experiments.

The ionic atmosphere around a nucleic acid regulates its stability in aqueous salt solutions. One major source of complexity in biological activities involving nucleic acids arises from the strong influence of the surrounding ions and water molecules on their structural and thermodynamic properties. Here, we implement a classical density functional theory for cylindrical polyelectrolytes embedded in aqueous electrolytes containing explicit (neutral hard sphere) water molecules at experimental solvent concentrations. Our approach allows us to include ion correlations as well as solvent and ion excluded volume effects for studying the structural and thermodynamic properties of highly charged cylindrical polyelectrolytes. Several models of size and charge asymmetric mixtures of aqueous electrolytes at physiological concentrations are studied. Our results are in good agreement with Monte Carlo simulations. Our numerical calculations display significant differences in the ion density profiles for the different aqueous electrolyte models studied. However, similar results regarding the excess number of ions adsorbed to the B-DNA molecule are predicted by our theoretical approach for different aqueous electrolyte models. These findings suggest that ion counting experimental data should not be used alone to validate the performance of aqueous DNA-electrolyte models.

Out of equilibrium ion distribution around a suspended particle undergoing electrophoretic motion

Abstract It is shown that the often used representations of the ionic atmosphere surrounding a charged spherical particle suspended in an electrolyte solution and moving with electrophoretic velocity under the action of an applied electric field are misleading at best. Numerical results for the actual out of equilibrium counterion, co-ion, total ion, and total charge density distributions are presented.

Anomalous power law decay in solvation dynamics of DNA: a mode coupling theory analysis of ion contribution

Several time dependent fluorescence Stokes shift (TDFSS) experiments have reported a slow power law decay in the hydration dynamics of a DNA molecule. Such a power law has neither been observed in computer simulations nor in some other TDFSS experiments. Here we observe that a slow decay may originate from collective ion contribution because in experiments DNA is immersed in a buffer solution, and also from groove bound water and lastly from DNA dynamics itself. In this work we first express the solvation time correlation function in terms of dynamic structure factors of the solution. We use mode coupling theory to calculate analytically the time dependence of collective ionic contribution. A power law decay in seen to originate from an interplay between long-range probe–ion direct correlation function and ion–ion dynamic structure factor. Although the power law decay is reminiscent of Debye–Falkenhagen effect, yet solvation dynamics is dominated by ion atmosphere relaxation times at longer length scales (small wave number) than in electrolyte friction. We further discuss why this power law may not originate from water motions which have been computed by molecular dynamics simulations. Finally, we propose several experiments to check the prediction of the present theoretical work.

Single-Molecule Methods for Ligand Counting: Linking Ion Uptake to DNA Hairpin Folding

Ligand associations play a significant role in biochemical processes, typically through stabilizing a particular conformation of a folded biomolecule. Here, we demonstrate the ability to measure the changes in the number of ligands associated with a single, stretched biomolecule as it undergoes a conformational change. We do this by combining thermodynamic theory with single-molecule measurements that directly track biomolecular conformation. We utilize this technique to determine the changes in the ionic atmosphere of a DNA hairpin undergoing a force-destabilized folding transition. We find that the number of counterions liberated upon DNA unfolding is a nonmonotonic function of the monovalent salt concentration of the solution, contrary to predictions from common nucleic acid models. This demonstrates that previously unobserved phenomena can be measured with our ligand counting approach.

Understanding Nucleic Acid–Ion Interactions

Ions surround nucleic acids in what is referred to as an ion atmosphere. As a result, the folding and dynamics of RNA and DNA and their complexes with proteins and with each other cannot be understood without a reasonably sophisticated appreciation of these ions' electrostatic interactions. However, the underlying behavior of the ion atmosphere follows physical rules that are distinct from the rules of site binding that biochemists are most familiar and comfortable with. The main goal of this review is to familiarize nucleic acid experimentalists with the physical concepts that underlie nucleic acid-ion interactions. Throughout, we provide practical strategies for interpreting and analyzing nucleic acid experiments that avoid pitfalls from oversimplified or incorrect models. We briefly review the status of theories that predict or simulate nucleic acid-ion interactions and experiments that test these theories. Finally, we describe opportunities for going beyond phenomenological fits to a next-generation, truly predictive understanding of nucleic acid-ion interactions.

Ion Counting from Explicit-Solvent Simulations and 3D-RISM

The ionic atmosphere around nucleic acids remains only partially understood at atomic-level detail. Ion counting (IC) experiments provide a quantitative measure of the ionic atmosphere around nucleic acids and, as such, are a natural route for testing quantitative theoretical approaches. In this article, we replicate IC experiments involving duplex DNA in NaCl(aq) using molecular dynamics (MD) simulation, the three-dimensional reference interaction site model (3D-RISM), and nonlinear Poisson-Boltzmann (NLPB) calculations and test against recent buffer-equilibration atomic emission spectroscopy measurements. Further, we outline the statistical mechanical basis for interpreting IC experiments and clarify the use of specific concentration scales. Near physiological concentrations, MD simulation and 3D-RISM estimates are close to experimental results, but at higher concentrations (>0.7 M), both methods underestimate the number of condensed cations and overestimate the number of excluded anions. The effect of DNA charge on ion and water atmosphere extends 20–25 Å from its surface, yielding layered density profiles. Overall, ion distributions from 3D-RISMs are relatively close to those from corresponding MD simulations, but with less Na+ binding in grooves and tighter binding to phosphates. NLPB calculations, on the other hand, systematically underestimate the number of condensed cations at almost all concentrations and yield nearly structureless ion distributions that are qualitatively distinct from those generated by both MD simulation and 3D-RISM. These results suggest that MD simulation and 3D-RISM may be further developed to provide quantitative insight into the characterization of the ion atmosphere around nucleic acids and their effect on structure and stability.

Crowding by Anionic Nanoparticles Causes DNA Double-Strand Instability and Compaction

Up to the present, DNA structural transitions caused by cationic polymers as well as in concentrated solutions of neutral polymers are well documented, while a little is known about DNA interaction with like-charge species. Herein, changes in the structure of DNA induced by anionic nanoparticles of different sizes (20-130 nm) were investigated by combining single-molecule DNA fluorescent microscopy, to monitor the conformational dynamics of long-chain DNA, with spectroscopic methods, to gain insight into changes in the secondary structure of DNA. The results showed that several percent of negatively charged silica nanoparticles induced DNA compaction from a coil to a globule, and this change was accompanied by a decrease in the melting temperature of the DNA double helix. DNA was compacted into toroidal condensates with reduced diameters of about 20-30 nm. Smaller 20 nm nanoparticles triggered a DNA coil-globule transition at lower concentrations, but the exclusion volume for each type of nanoparticle at the point of complete DNA collapse, as estimated by taking into account the depth of the ionic atmosphere, was found to be almost the same.

The Physics of DNA in Confinement

Throughout all kingdoms of life, DNA is found to form compact structures. DNA is neatly wound inside a viral capsid, DNA forms hierarchical structures in cell nuclei, DNA could even be woven into complex 3D structures known as DNA origami. Such a ubiquitous compaction is surprising, as it contradicts, at the first look, the very basic physical properties of DNA: the high electrostatic charge and resistance to bending at the scale of 50 nm or less. Experimental work has shown that counterions surrounding DNA can considerably alter its properties, for example, turning electrostatic self-repulsion into attraction. Yet, elucidating the precise microscopic structure and mechanism of DNA-DNA interaction in confined environment remains beyond the experimental capability. Here, we report the results of all-atom molecular dynamics simulations that investigated the microscopic structure of dense DNA assemblies and the physics of interactions that makes such assemblies possible. First, we show that a refined parameterization of ion-DNA interaction [1] permits the all-atom MD method to quantitatively reproduce experimentally known properties [2,3] of dense DNA arrays. Next we characterize the microscopic structure of the arrays, elucidating their ionic atmosphere, preferred azimuthal orientation of DNA molecules, the pair-wise additivity of DNA-DNA forces, the longitudinal friction forces between DNA molecules, and the role of solvation force. Our study demonstrates the ability of all-atom molecular dynamics simulations to provide quantitative, accurate information about dense DNA systems, opening exciting opportunities for future work in the area of synthetic DNA nanostructures, DNA packaging in viral capsids and cell nuclei.[1] J Phys Chem Lett 3:45-50.[2] Proc Natl Acad Sci U S A 81:2621-2625.[3] Biophys J 94:4775-82.

Sorting Out the Structure of Single-Stranded DNA

The mechanical properties of single stranded nucleic acids play a vital role in such dynamic processes as DNA replication and RNA folding. While experiments have demonstrated that duplex DNA molecules behave as ideal worm-like chains with a persistence length that can be measured accurately, the unfolded single-stranded form of DNA (ssDNA) has been surprisingly recalcitrant: different biophysical techniques lead to different conclusions. Making matters worse, all-atom molecular dynamics simulations of ssDNA do not agree with experiment. This has motivated new experimental and theoretical work. In recent force spectroscopy and computational studies, McIntosh, Stevens and Saleh propose models where excluded volume influences long-ranged structure, while specific ion interactions induce wrinkles at short length scales (Single-stranded DNA is not a wormlike-chain, Biophys. J. 104, 28). However, direct structural evidence for these models is lacking. Thus, we perform detailed investigations of ssDNA homopolymers using x-ray scattering, single molecule FRET, and quantitative characterization of the ion atmosphere in mono- and di-valent salt. We develop a novel data-driven ensemble optimization technique that allows us to visualize the conformational adaptation of the DNA backbone to changes in the ion atmosphere, including the distinct effects of base stacking and ion valence. Correlation functions obtained from the structure ensembles, without reference to polymer or electrostatic theories, nonetheless show signatures of electrostatic excluded volume and strong ion effects at short distances. We discuss the implications for new polyelectrolyte theories of ssDNA and the biological role of electrostatics in these systems.

Aging effects of anatase TiO2 nanoparticles in Li-ion batteries

Anatase TiO2 nanoparticles with a diameter of 5 nm have been investigated as a negative intercalation electrode material for Li-ion batteries. The focus was on the stability upon cycling within four different potential ranges, namely from 1.5, 1.2, 1.0 and 0.7 V vs. Li/Li(+) as the lower potential limit to 3.0 V vs. Li/Li(+) as the upper potential limit. While a lower cut-off potential allows for a higher amount of charge stored, the irreversible processes induce a faster fading of the specific charge. Galvanostatic cycling (GC), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) experiments suggest that SEI formation has a negligible contribution to the irreversible processes. It appears more plausible that an irreversible degradation of the bulk phase occurs, leading to a decrease in the amount of active sites. Moreover, it has been observed that this degradation appears as an anodic shift of the thermodynamic potential of (de-)intercalation of Li-ions in the TiO2 structure. The shift is caused by a change in the activity of Li-ions in the solid phase, which is driven by changes in the ionic atmosphere of the crystal.

The Snakelike Chain Character of Unstructured RNA

The three-dimensional conformation of RNA is governed by a number of physical and chemical factors. However, in the absence of base-pairing and tertiary structure, unstructured RNA assumes a random-walk conformation dominated by the electrostatic self-repulsion of its charged, flexible backbone. This behavior is often modeled as a “wormlike chain” (WLC) with an electrostatics-dependent persistence length. However, through measurements of the end-to-end extension and ion atmosphere of poly(U) RNA stretched by 0.1-10 pN applied force, we find that the WLC model does not adequately describe the behavior of unstructured RNA. Instead, we find that our data are well described by a “snakelike chain” (SLC) model. The SLC model is characterized by smooth bending on long length scales and ion-stabilized crumpling on short length scales. We see signatures of both regimes in our extension vs. force data: a low-force power-law characteristic of a chain of swollen blobs on long length scales and a high-force region of increasing compliance with ion valence, consistent with increased conformational stabilization, on short length scales. In monovalent salt, we find the crossover between the two regimes (SLC blob size) to scale with the Debye screening length, indicating the determining importance of electrostatics. By systematically varying force and bulk salt concentration, we measure the change in the number of ions associated with the RNA as it is stretched. We find that ions are liberated during stretching. This is consistent with the SLC picture: ions that stabilize the short-length-scale crumples are released when those crumples are mechanically straightened. Additionally, we observe the number of ions liberated increases with increasing bulk salt concentration; this is consistent with the SLC model, but contradicts the WLC model with electrostatics-dependent persistence length.