Understanding temperature-modulated calorimetry through studies of a model system.

Temperature modulated calorimetry is widely used but still raises some fundamental questions. In this paper we study a model system as a test sample to address some of them. The model has a nontrivial spectrum of relaxation times. We investigate temperature-modulated calorimetry at constant average temperature to precise the meaning of the frequency-dependent heat capacity, its relation with entropy production, and how such measurements can observe the aging of a glassy sample leading to a time-dependent heat capacity. The study of the Kovacs effect for an out-of-equilibrium system shows how temperature-modulated calorimetry could contribute to the understanding of this memory effect. Then we compare measurements of standard scanning calorimetry and temperature-modulated calorimetry and show how the two methods are complementary because they do not observe the same features. While it can probe the timescales of energy transfers in a system, even in the limit of low-frequency temperature-modulated calorimetry does not probe some relaxation phenomena which can be measured by scanning calorimetry, as suggested by experiments with glasses.

Melting transition of oriented Li-DNA fibers submerged in ethanol solutions.

The melting transition of Li-DNA fibers immersed in ethanol-water solutions has been studied using calorimetry and neutron diffraction techniques. The data have been analyzed using the Peyrard-Bishop-Dauxois model to determine the strengths of the intra- and inter-base pair potentials. The data and analysis show that the potentials are weaker than those for DNA in water. They become weaker still and the DNA less stable as the ethanol concentration increases but, conversely, the fibers become more compact and the distances between base pairs become more regular. The results show that the melting transition is relatively insensitive to local confinement and depends more on the interaction between the DNA and its aqueous environment.

Memory effects in glasses: Insights into the thermodynamics of out-of-equilibrium systems revealed by a simple model of the Kovacs effect.

Glasses are interesting materials because they allow us to explore the puzzling properties of out-of-equilibrium systems. One of them is the Kovacs effect in which a glass, brought to an out-of-equilibrium state in which all its thermodynamic variables are identical to those of an equilibrium state, nevertheless evolves, showing a hump in some global variable before the thermodynamic variables come back to their starting point. We show that a simple three-state system is sufficient to study this phenomenon using numerical integrations and exact analytical calculations. It also brings some light on the concept of fictive temperature, often used to extend standard thermodynamics to the out-of-equilibrium properties of glasses. We confirm that the concept of a unique fictive temperature is not valid, an show it can be extended to make a connection with the various relaxation processes in the system. The model also brings further insights on the thermodynamics of out-of-equilibrium systems. Moreover, we show that the three-state model is able to describe various effects observed in glasses such as the asymmetric relaxation to equilibrium discussed by Kovacs, or the reverse crossover measured on B_{2}O_{3}.

How is information transmitted in a nerve?

In the last 15 years, a debate has emerged about the validity of the famous Hodgkin-Huxley model for nerve impulse. Mechanical models have been proposed. This note reviews the experimental properties of the nerve impulse and discusses the proposed alternatives. The experimental data, which rule out some of the alternative suggestions, show that while the Hodgkin-Huxley model may not be complete, it nevertheless includes essential features that should not be overlooked in the attempts made to improve, or supersede, it.

Comment on "Dynamically induced heat rectification in quantum systems".

The article by Riera-Campeny, Mehboudi, Pons, and Sanpera [Phys. Rev. E 99, 032126 (2019)2470-004510.1103/PhysRevE.99.032126] studies heat rectification in a network of harmonic oscillators which is periodically driven. Both the title and introduction stress the quantum nature of the system. Here we show that the results are more general and are equally valid for a classical system, which broadens the interest of the paper and may suggest further pathways for a basic understanding of the phenomenon.

Melting Transition of Oriented DNA Fibers Submerged in Poly(ethylene glycol) Solutions Studied by Neutron Scattering and Calorimetry.

The influence of molecular confinement on the melting transition of oriented Na-DNA fibers submerged in poly(ethylene glycol) (PEG) solutions has been studied. The PEG solution exerts an osmotic pressure on the fibers which, in turn, is related to the DNA intermolecular distance. Calorimetry measurements show that the melting temperature increases and the width of the transition decreases with decreasing intermolecular distance. Neutron scattering was used to monitor the integrated intensity and width of a Bragg peak from the B-form of DNA as a function of temperature. The data were quantitatively analyzed using the Peyrard-Bishop-Dauxois model. The experiments and analysis showed that long segments of double-stranded DNA persist until the last stages of melting and that there appears to be a substantial increase of the DNA dynamics as the melting temperature of the DNA is approached.

Melting of highly oriented fiber DNA subjected to osmotic pressure.

A pilot study of the possibility to investigate temperature-dependent neutron scattering from fiber-DNA in solution is presented. The study aims to establish the feasibility of experiments to probe the influence of spatial confinement on the structural correlation and the formation of denatured bubbles in DNA during the melting transition. Calorimetry and neutron scattering experiments on fiber samples immersed in solutions of poly(ethylene glycol) (PEG) prove that the melting transition occurs in these samples, that the transition is reversible to some degree, and that the transition is broader in temperature than for humidified fiber samples. The PEG solutions apply an osmotic pressure that maintains the fiber orientation, establishing the feasibility of future scattering experiments to study the melting transition in these samples.

Ionic mobility in DNA films studied by dielectric spectroscopy.

Double-helix DNA molecules can be found under different conformational structures driven by ionic and hydration surroundings. Usually, only the B-form of DNA, which is the only form stable in aqueous solution, can be studied by dielectric measurements. Here, the dielectric responses of DNA molecules in the A- and B-form, oriented co-linearly within fibres assembled in a film have been analyzed. The dielectric dispersion, permittivity and dissipation factor, have been measured as a function of frequency, strength voltage, time, temperature and nature of the counter-ions. Besides a high electrode polarization component, two relaxation peaks have been observed and fitted by two Cole-Cole relaxation terms. In the frequency range that we investigated (0.1 Hz to 5 ·10(6) Hz) the dielectric properties are dominated by the mobility and diffusivity of the counter-ions and their interactions with the DNA molecules, which can therefore be characterized for the A- and B-forms of DNA.

Characterization of the low-temperature properties of a simplified protein model.

Prompted by results that showed that a simple protein model, the frustrated Go model, appears to exhibit a transition reminiscent of the protein dynamical transition, we examine the validity of this model to describe the low-temperature properties of proteins. First, we examine equilibrium fluctuations. We calculate its incoherent neutron-scattering structure factor and show that it can be well described by a theory using the one-phonon approximation. By performing an inherent structure analysis, we assess the transitions among energy states at low temperatures. Then, we examine nonequilibrium fluctuations after a sudden cooling of the protein. We investigate the violation of the fluctuation-dissipation theorem in order to analyze the protein glass transition. We find that the effective temperature of the quenched protein deviates from the temperature of the thermostat, however it relaxes towards the actual temperature with an Arrhenius behavior as the waiting time increases. These results of the equilibrium and nonequilibrium studies converge to the conclusion that the apparent dynamical transition of this coarse-grained model cannot be attributed to a glassy behavior.

Temperature dependence of the DNA double helix at the nanoscale: structure, elasticity, and fluctuations.

Biological organisms exist over a broad temperature range of -15°C to +120°C, where many molecular processes involving DNA depend on the nanoscale properties of the double helix. Here, we present results of extensive molecular dynamics simulations of DNA oligomers at different temperatures. We show that internal basepair conformations are strongly temperature-dependent, particularly in the stretch and opening degrees of freedom whose harmonic fluctuations can be considered the initial steps of the DNA melting pathway. The basepair step elasticity contains a weaker, but detectable, entropic contribution in the roll, tilt, and rise degrees of freedom. To extend the validity of our results to the temperature interval beyond the standard melting transition relevant to extremophiles, we estimate the effects of superhelical stress on the stability of the basepair steps, as computed from the Benham model. We predict that although the average twist decreases with temperature in vitro, the stabilizing external torque in vivo results in an increase of ∼1°/bp (or a superhelical density of Δσ ≃ +0.03) in the interval 0-100°C. In the final step, we show that the experimentally observed apparent bending persistence length of torsionally unconstrained DNA can be calculated from a hybrid model that accounts for the softening of the double helix and the presence of transient denaturation bubbles. Although the latter dominate the behavior close to the melting transition, the inclusion of helix softening is important around standard physiological temperatures.

Purification of A-form DNA fiber samples by the removal of B-form DNA residues.

To date, fiber diffraction on A-form NaDNA has always shown a B-form contamination. Here we have used optic microscopy, calorimetry, and neutron scattering techniques to define a method to obtain DNA fibres samples whose molecules are purely in the A-form. When the impure sample is heated to 320 K, the DNA molecules in the B-form undergo a transition into the A-form. Our studies have modified the accepted phase diagram for NaDNA films by including the dependence of temperature crucial for the purification of A-form samples by removal of B-form contamination.

Base pair openings and temperature dependence of DNA flexibility.

The relationship of base pair openings to DNA flexibility is examined. Published experimental data on the temperature dependence of the persistence length by two different groups are well described in terms of an inhomogeneous Kratky-Porot model with soft and hard joints, corresponding to open and closed base pairs, and sequence-dependent statistical information about the state of each pair provided by a Peyrard-Bishop-Dauxois (PBD) model calculation with no freely adjustable parameters.

Glassy behavior of denatured DNA films studied by differential scanning calorimetry.

We use differential scanning calorimetry (DSC) to study the properties of DNA films, made of oriented fibers, heated above the thermal denaturation temperature of the double helical form. The films show glassy properties that we investigate in two series of experiments, a slow cooling at different rates followed by a DSC scan upon heating and aging at a temperature below the glass transition. Introducing the fictive temperature to characterize the glass allows us to derive quantitative information on the relaxations of the DNA films, in particular to evaluate their enthalpy barrier. A comparison with similar aging studies on PVAc highlights some specificities of the DNA samples.

Structural correlations and melting of B-DNA fibers.

Despite numerous attempts, understanding the thermal denaturation of DNA is still a challenge due to the lack of structural data on the transition since standard experimental approaches to DNA melting are made in solution and do not provide spatial information. We report a measurement using neutron scattering from oriented DNA fibers to determine the size of the regions that stay in the double-helix conformation as the melting temperature is approached from below. A Bragg peak from the B form of DNA is observed as a function of temperature and its width and integrated intensity are measured. These results, complemented by a differential calorimetry study of the melting of B-DNA fibers as well as electrophoresis and optical observation data, are analyzed in terms of a one-dimensional mesoscopic model of DNA.

Thermal denaturation of DNA studied with neutron scattering.

The melting transition of DNA, whereby the strands of the double-helix structure completely separate at a certain temperature, has been characterized using neutron scattering. A Bragg peak from B-form fiber DNA has been measured as a function of temperature, and its widths and integrated intensities have been interpreted using the Peyrard-Bishop-Dauxois model with only one free parameter. The experiment is unique, as it gives spatial correlation along the molecule through the melting transition where other techniques cannot.

Guanine radical chemistry reveals the effect of thermal fluctuations in gene promoter regions.

DNA is not the static entity that structural pictures suggest. It has been longly known that it 'breathes' and fluctuates by local opening of the bases. Here we show that the effect of structural fluctuations, exhibited by AT-rich low stability regions present in some common transcription initiation regions, influences the properties of DNA in a distant range of at least 10 bp. This observation is confirmed by experiments on genuine gene promoter regions of DNA. The spatial correlations revealed by these experiments throw a new light on the physics of DNA and could have biological implications, for instance by contributing to the cooperative effects needed to assemble the molecular machinery that forms the transcription complex.

Critical examination of the inherent-structure-landscape analysis of two-state folding proteins.

Recent studies attracted the attention on the inherent-structure-landscape (ISL) approach as a reduced description of proteins allowing to map their full thermodynamic properties. However, the analysis has been so far limited to a single topology of a two-state folding protein, and the simplifying assumptions of the method have not been examined. In this work, we construct the thermodynamics of four two-state folding proteins of different sizes and secondary structure by molecular dynamics (MD) simulations using the ISL method and critically examine possible limitations of the method. Our results show that the ISL approach correctly describes the thermodynamics function, such as the specific heat, on a qualitative level. Using both analytical and numerical methods, we show that some quantitative limitations cannot be overcome with enhanced sampling or the inclusion of harmonic corrections.

Modeling protein thermodynamics and fluctuations at the mesoscale.

We use an extended Go model, in unfrustrated and frustrated variants, to study the energy landscape and the fluctuations of a model protein. The model exhibits two transitions, folding and dynamical transitions, when changing the temperature. The inherent structures corresponding to the minima of the landscape are analyzed and we show how their energy density can be obtained from simulations around the folding temperature. The scaling of this energy density is found to reflect the folding transition. Moreover, this approach allows us to build a reduced thermodynamics in the inherent structure landscape. Equilibrium studies, from full molecular dynamics (MD) simulations and from the reduced thermodynamics, detect the features of a dynamical transition at low temperature and we analyze the location and time scale of the fluctuations of the protein, showing the need of some frustration in the model to get realistic results. The frustrated model also shows the presence of a kinetic trap which strongly affects the dynamics of folding.

The inherent structure landscape of a protein.

Using the Go model of a real protein, we explore the landscape of its metastable structures. First, we show how the inherent structure energy density can be obtained from the probability density determined by sampling molecular dynamics trajectories and quenching. The analysis of the inherent structure landscape can characterize the folding transition. Then we show how thermodynamics of the inherent states can be established to study the equilibrium properties of proteins. Our work brings some elements into the current discussion about the protein dynamical transition. The study uses a simplified model to illustrate the ideas, but, as the inherent structure landscape is much simpler than the free energy surface of the protein, it appears to be accessible for an all-atom model of a small protein, at the expense of much longer calculations.