Nonlocal Dielectric Response of Water in Nanoconfinement.

Recent experiments reporting a very low dielectric permittivity for nanoconfined water have renewed the interest in the structure and dielectric properties of water in narrow gaps. Here, we describe such systems with a minimal Landau-Ginzburg field theory composed of a nonlocal bulk-determined term and a local water-surface interaction term. We show how the interplay between the boundary conditions and intrinsic bulk correlations encodes the dielectric properties of confined water. Our theoretical analysis is supported by molecular dynamics simulations and comparison with the experimental data.

Dielectric response in the vicinity of an ion: A nonlocal and nonlinear model of the dielectric properties of water.

The goal of this work is to propose a simple continuous model that captures the dielectric properties of water at the nanometric scale. We write an electrostatic energy as a functional of the polarisation field containing a term in P4 and non-local Gaussian terms. Such a hamiltonian can reproduce two key properties of water: the saturation of the polarisation response of water in the presence of a strong electrostatic field and the nanometric dipolar correlations of the solvent molecules modifying the long range van der waals interaction. This model explores thus two fundamental aspects that have to be included in implicit models of electrolytes for a relevant description of electrostatic interactions at nanometric scales.

Gaussian field model for polar fluids as a function of density and polarization: Toward a model for water.

This work is concerned with a simple model for a polar fluid, a Gaussian field model based on the excess density and on the polarization. It is a convenient framework to implement the dielectric properties of correlated liquids that stem from nanometric correlations between molecules. It allows us to study the effects of coupling terms between density and polarization on the structure of the fluid. Despite the simplicity of such a model, it can capture some interesting features of the response functions of water such as the quasi-resonant longitudinal dielectric susceptibility or the presence of two maxima in the structure factor. Explicit models of water generate high computational cost and implicit models sometimes fail to properly treat the electrostatic interactions. A Gaussian field theory could therefore be an interesting alternative to describe water.

Fluctuations in reactive networks subject to extrinsic noise studied in the framework of the chemical Langevin equation.

Theoretical and experimental studies have shown that the fluctuations of in vivo systems break the fluctuation-dissipation theorem. One can thus ask what information is contained in the correlation functions of protein concentrations and how they relate to the response of the reactive network to a perturbation. Answers to these questions are of prime importance to extract meaningful parameters from the in vivo fluorescence correlation spectroscopy data. In this paper we study the fluctuations of the concentration of a reactive species involved in a cyclic network that is in a nonequilibrium steady state perturbed by a noisy force, taking into account both the breaking of detailed balance and extrinsic noises. Using a generic model for the network and the extrinsic noise, we derive a chemical Langevin equation that describes the dynamics of the system, we determine the expressions of the correlation functions of the concentrations, and we estimate the deviation of the fluctuation-dissipation theorem and the range of parameters in which an effective temperature can be defined.

Fluctuation-induced forces governed by the dielectric properties of water-A contribution to the hydrophobic interaction.

The hydrophobic interaction between objects immersed in water is typically attractive and adds to the well-known van der Waals interaction. The former supposedly dominates the latter on nanometric distances and could be of major importance in the assembly of biologic objects. Here, we show that the fluctuation-induced attraction between two objects immersed in a correlated dielectric medium which models water is the sum of a van der Waals term and a short-range contribution that can be identified as part of the hydrophobic interaction. In this framework, we calculate analytically the fluid correlation function and the fluctuation-induced interaction between small and extended inclusions embedded in water and we characterize the hydrophobic terms.

Chemical mechanism identification from frequency response to small temperature modulation.

The description of interactions between biochemical species and the elucidation of the corresponding chemical mechanisms encounter an increasing interest both for the comprehension of biological pathways at the molecular scale and for the rationalization of drug design. Relying on powerful experimental tools such as thermal microfluidics and fluorescence detection, we propose a methodology to determine the chemical mechanism of a reaction without fitting parameters. A mechanism consistent with the accessible knowledge is assumed, and the assumption is checked through an iterative protocol. The test is based on the frequency analysis of the response of a targeted reactive species to temperature modulation. We build specific functions of the frequency that are constant for the assumed mechanism and show that the graph of these functions can be drawn from appropriate data analysis. The method is general and can be applied to any complex mechanism. It is here illustrated in detail in the case of single relaxation time mechanisms.

Temperature modulation and quadrature detection for selective titration of two-state exchanging reactants.

Biological samples exhibit huge molecular diversity over large concentration ranges. Titrating a given compound in such mixtures is often difficult, and innovative strategies emphasizing selectivity are thus demanded. To overcome limitations inherent to thermodynamics, we here present a generic technique where discrimination relies on the dynamics of interaction between the target of interest and a probe introduced in excess. Considering an ensemble of two-state exchanging reactants submitted to temperature modulation, we first demonstrate that the amplitude of the out-of-phase concentration oscillations is maximum for every compound involved in a reaction whose equilibrium constant is equal to unity and whose relaxation time is equal to the inverse of the excitation angular frequency. Taking advantage of this feature, we next devise a highly specific detection protocol and validate it using a microfabricated resistive heater and an epifluorescence microscope, as well as labeled oligonucleotides to model species displaying various dynamic properties. As expected, quantification of a sought for strand is obtained even if interfering reagents are present in similar amounts. Moreover, our approach does not require any separation and is compatible with imaging. It could then benefit some of the numerous binding assays performed every day in life sciences.

Determination of the six rate constants of a three-state enzymatic network and a noninvasive test of detailed balance.

The Michaelis-Menten mechanism is unanimously recognized by experimentalists and theoreticians as the reference model for the description of enzymatic catalysis. The recent explosion in the diversity of fluorescent probes solves the problem of in situ observation of proteins and the experimental investigation of enzymatic dynamics, which determines the Michaelis constant or a small number of relaxation times, is becoming more and more common. We propose a protocol for the full characterization of enzyme kinetics in the framework of the Michaelis-Menten mechanism. The method relies on the measurement of the oscillation amplitude of the enzymatic concentrations, when the biological medium is submitted to a temperature modulation of a few degrees. Analytical expressions of all the rate constants as functions of the concentration amplitudes are derived. The noninvasive character of the perturbation and the assessable uncertainty on the rate constant values make an in situ test of detailed balance possible.

Resonant response to temperature modulation for enzymatic dynamics characterization.

We consider enzymes involved in a three-state Michaelis-Menten kinetics and submitted to well-chosen temperature modulations of small amplitude. From the first-order amplitudes of concentration oscillations, we design a response function that is maximum for targeted values of the chemical relaxation times. This resonant function can be used to screen a large set of enzymes and identify the one governed by the desired kinetics. The method gives access to all the dynamical parameters of the targeted enzyme without resorting to a fit. We show how to estimate the precision of this parameter determination and give some hints for experimental validation.

Fourier analysis to measure diffusion coefficients and resolve mixtures on a continuous electrophoresis chip.

We report a method to measure diffusion coefficients of fluorescent solutes in the 10(2)-10(6) Da molecular mass range in a glass-PDMS chip. Upon applying a permanent electric field, the solute is introduced through a narrow channel into a wide analysis chamber where it migrates along the injection axis and diffuses in two dimensions. The diffusion coefficient is extracted after 1D Fourier transform of the resulting stationary concentration pattern. Analysis is straightforward, requiring no numerical integration or velocity field simulation. The diffusion coefficients measured for fluorescein, rhodamine green-labeled oligonucleotides, and YOYO-1-stained dsDNA fragments agree with the literature values and with our own fluorescence correlation spectroscopy measurements. As shown for 151 and 1257 base pair dsDNA mixtures, the present method allows us to rely on diffusion to quantitatively characterize the nature and the composition of binary mixtures. In particular, we implement a DNA hybridization assay to illustrate the efficiency of the proposed protocol for library screening.

Temporal modulation of a spatially periodic potential for kinetically governed oriented motion.

This theoretical paper introduces an experimental protocol derived from the concept of Brownian motors in order to selectively confer an oriented motion to given charged reactants. Instead of maintaining permanently the system in nonequilibrium conditions, we propose a simple experimental trick to restore periodically a transient out-of-equilibrium regime: the reactive medium is alternately submitted to a sawtooth potential and to a potential ramp. The model provides approximate analytical expressions for the operating conditions allowing us to design the extraction from a mixture of any desired reactant characterized by its rate constants. The orders of magnitude suggest a possible implementation in microsystems where the present approach could be used for separation and analysis.

Response to a temperature modulation as a signature of chemical mechanisms.

We consider n reactive species involved in unimolecular reactions and submitted to a temperature modulation of small amplitude. We determine the conditions on the rate constants for which the deviations from the equilibrium concentrations of each species can be optimized and find the analytical expression of the frequency associated with an extremum of concentration shift in the case n=3. We prove that the frequency dependence of the displacement of equilibrium gives access to the number n of species involved in the mechanism. We apply the results to the case of the transformation of a reactant into a product through a possible reactive intermediate and find the order relation obeyed by the activation energies of the different barriers. The results typically apply to enzymatic catalysis with kinetics of Michaelis-Menten type.