Biomedical subjects

F Ritort

Publications and source records attributed to F Ritort.

At least 19 recordsLinked to original sources

PubMed2006

Force-dependent fragility in RNA hairpins.

We apply Kramers theory to investigate the dissociation of multiple bonds under mechanical force and interpret experimental results for the unfolding and refolding force distributions of an RNA hairpin pulled at different loading rates using laser tweezers. We identify two different kinetic regimes depending on the range of forces explored during the unfolding and refolding process. The present approach extends the range of validity of the two-states approximation by providing a theoretical framework to reconstruct free-energy landscapes and identify force-induced structural changes in molecular transition states using single molecule pulling experiments. The method should be applicable to RNA hairpins with multiple kinetic barriers.

Computer Simulation↗

PubMed2006

Condensation transition in DNA-polyaminoamide dendrimer fibers studied using optical tweezers.

When mixed together, DNA and polyaminoamide dendrimers form fibers that condense into a compact structure. We use optical tweezers to pull condensed fibers and investigate the decondensation transition by measuring force-extension curves (FECs). A characteristic force plateau (around 10 pN) and hysteresis between the pulling and relaxation cycles are observed for different dendrimer sizes, indicating the existence of a first-order transition between two phases (condensed and extended) of the fiber. Upon salt variation FECs change noticeably confirming that electrostatic forces drive the condensation transition. We propose a simple model for the decondensing transition that qualitatively reproduces the FECs and which is confirmed by atomic force microscopy images.

Bacteriophage lambda↗

PubMed2005

Universality of fluctuation-dissipation ratios: the ferromagnetic model.

We calculate analytically the fluctuation-dissipation ratio (FDR) for Ising ferromagnets quenched to criticality, both for the long-range model and its short-range analog in the limit of large dimension. Our exact solution shows that, for both models, if the system is unmagnetized while if the initial magnetization is nonzero. This indicates that two different classes of critical coarsening dynamics need to be distinguished depending on the initial conditions, each with its own nontrivial FDR. We also analyze the dependence of the FDR on whether local and global observables are used. These results clarify how a proper local FDR (and the corresponding effective temperature) should be defined in long-range models in order to avoid spurious inconsistencies and maintain the expected correspondence between local and global results; global observables turn out to be far more robust tools for detecting nonequilibrium FDRs.

Journal Article↗

PubMed2005

Mode-dependent nonequilibrium temperature in aging systems.

We introduce an exactly solvable model for glassy dynamics with many relaxational modes, each one characterized by a different relaxational time scale. Analytical solution of the aging dynamics at low temperatures shows that a nonequilibrium or effective temperature can be associated to each time scale or mode. The spectrum of effective temperatures shows two regions that are separated by an age-dependent boundary threshold. Region I is characterized by partially equilibrated modes that relax faster than the modes at the threshold boundary. Thermal fluctuations and time correlations for modes in region I show that those modes are in mutual thermal equilibrium at a unique age-dependent effective temperature theta(s). In contrast, modes with relaxational time scales longer than that of modes at the threshold (region II) show diffusive properties and do not share the common temperature theta(s). The shift of the threshold toward lower energy modes as the system ages, and the progressive shrinking of region II, determines how the full spectrum of modes equilibrates. As is usually done in experiments, we have defined a frequency-dependent effective temperature and we have found that all modes in region I are mutually equilibrated at the temperature theta(s) independently of the probing frequency. The present model aims to explain transport anomalies observed in supercooled liquids in terms of a collection of structurally disordered and cooperative rearranging mesoscopic regions.

Journal Article↗

PubMed2005

Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies.

Atomic force microscopes and optical tweezers are widely used to probe the mechanical properties of individual molecules and molecular interactions, by exerting mechanical forces that induce transitions such as unfolding or dissociation. These transitions often occur under nonequilibrium conditions and are associated with hysteresis effects-features usually taken to preclude the extraction of equilibrium information from the experimental data. But fluctuation theorems allow us to relate the work along nonequilibrium trajectories to thermodynamic free-energy differences. They have been shown to be applicable to single-molecule force measurements and have already provided information on the folding free energy of a RNA hairpin. Here we show that the Crooks fluctuation theorem can be used to determine folding free energies for folding and unfolding processes occurring in weak as well as strong nonequilibrium regimes, thereby providing a test of its validity under such conditions. We use optical tweezers to measure repeatedly the mechanical work associated with the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. The resultant work distributions are then analysed according to the theorem and allow us to determine the difference in folding free energy between an RNA molecule and a mutant differing only by one base pair, and the thermodynamic stabilizing effect of magnesium ions on the RNA structure.

Base Pairing↗

PubMed2005

Resonant nonequilibrium temperatures.

In this paper, we investigate nonequilibrium temperatures in a two-state system driven to a nonequilibrium steady state by the action of an oscillatory field. The nonequilibrium temperature is determined by coupling a small cavity or probe to the nonequilibrium system and studying the fluctuating noise in the cavity, as has been proposed in the context of glassy systems. We show the presence of resonant effects in the nonequilibrium temperature and discuss the existence of a constitutive steady-state equation in such nonequilibrium conditions. We propose this simple model as an excellent system to carry out experimental measurements of nonequilibrium temperatures. This may help to better understand the physical meaning of such an elusive concept.

Journal Article↗

PubMed2005

Thermodynamic and kinetic aspects of RNA pulling experiments.

Recent single-molecule pulling experiments have shown how it is possible to manipulate RNA molecules using laser tweezers. In this article we investigate a minimal model for the experimental setup which includes an RNA molecule connected to two polymers (handles) and a bead trapped in the optical potential and attached to one of the handles. We start by considering the case of small single-domain RNA molecules, which unfold in a cooperative way. The model qualitatively reproduces the experimental results and allows us to investigate the influence of the bead and handles on the unfolding reaction. A main ingredient of the model is to consider the appropriate statistical ensemble and the corresponding thermodynamic potential describing thermal fluctuations in the system. We then investigate several questions relevant to extract thermodynamic information from experimental data. The kinetics of unfolding is also studied by introducing a dynamical model. Finally, we apply the model to the more general problem of a multidomain RNA molecule with Mg(2+) tertiary contacts that unfolds in a sequential way.

Biophysics↗

PubMed2004

Experimental test of Hatano and Sasa's nonequilibrium steady-state equality.

Most natural processes occur far from equilibrium and cannot be treated within the framework of classical thermodynamics. In 1998, Oono and Paniconi [Oono, Y. & Paniconi, M. (1998) Prog. Theor. Phys. Suppl. 130, 29-44] proposed a general phenomenological framework, steady-state thermodynamics, encompassing nonequilibrium steady states and transitions between such states. In 2001, Hatano and Sasa [Hatano, T. & Sasa, S. (2001) Phys. Rev. Lett. 86, 3463-3466] derived a testable prediction of this theory. Specifically, they were able to show that the exponential average of Y, a quantity similar to a dissipated work, should be equal to zero for arbitrary transitions between nonequilibrium steady states, -ln = 0. We have tested this strong prediction by measuring the dissipation and fluctuations of microspheres optically driven through water. We have found that -ln approximately 0 for three different nonequilibrium systems, supporting Hatano and Sasa's proposed extension of thermodynamics to arbitrary steady states and irreversible transitions.

Models, Theoretical↗

PubMed2002

A two-state kinetic model for the unfolding of single molecules by mechanical force.

We investigate the work dissipated during the irreversible unfolding of single molecules by mechanical force, using the simplest model necessary to represent experimental data. The model consists of two levels (folded and unfolded states) separated by an intermediate barrier. We compute the probability distribution for the dissipated work and give analytical expressions for the average and variance of the distribution. To first order, the amount of dissipated work is directly proportional to the rate of application of force (the loading rate) and to the relaxation time of the molecule. The model yields estimates for parameters that characterize the unfolding kinetics under force in agreement with those obtained in recent experimental results. We obtain a general equation for the minimum number of repeated experiments needed to obtain an equilibrium free energy, to within k(B)T, from nonequilibrium experiments by using the Jarzynski formula. The number of irreversible experiments grows exponentially with the ratio of the average dissipated work, W(dis) to k(B)T.

Biomechanical Phenomena↗

PubMed2002

Disordered backgammon model.

In this paper we consider an exactly solvable model that displays glassy behavior at zero temperature due to entropic barriers. The new ingredient of the model is the existence of different energy scales or modes associated with different relaxational time scales. Low-temperature relaxation takes place by partial equilibration of successive lower-energy modes. An adiabatic scaling solution, defined in terms of a threshold energy scale epsilon*, is proposed. For such a solution, modes with energy epsilon>>epsilon* are equilibrated at the bath temperature, modes with epsilon<<epsilon* remain out of equilibrium, and relaxation occurs in the neighborhood of the threshold epsilon approximately epsilon*. The model is presented as a toy example to investigate the conditions related to the existence of an effective temperature in glassy systems and its possible dependence on the energy sector is probed by the corresponding observable.

Journal Article↗

PubMed1999

Damage spreading transition in glasses: a probe for the ruggedness of the configurational landscape.

We consider damage spreading transitions in the framework of mode-coupling theory. This theory describes relaxation processes in glasses in the mean-field approximation which are known to be characterized by the presence of an exponentially large number of metastable states. For systems evolving under identical but arbitrarily correlated noises, we demonstrate that there exists a critical temperature T0 which separates two different dynamical regimes depending on whether damage spreads or not in the asymptotic long-time limit. This transition exists for generic noise correlations such that the zero damage solution is stable at high temperatures, being minimal for maximal noise correlations. Although this dynamical transition depends on the type of noise correlations, we show that the asymptotic damage has the good properties of a dynamical order parameter, such as (i) independence of the initial damage; (ii) independence of the class of initial condition; and (iii) stability of the transition in the presence of asymmetric interactions which violate detailed balance. For maximally correlated noises we suggest that damage spreading occurs due to the presence of a divergent number of saddle points (as well as metastable states) in the thermodynamic limit consequence of the ruggedness of the free-energy landscape which characterizes the glassy state. These results are then compared to extensive numerical simulations of a mean-field glass model (the Bernasconi model) with Monte Carlo heat-bath dynamics. The freedom of choosing arbitrary noise correlations for Langevin dynamics makes damage spreading an interesting tool to probe the ruggedness of the configurational landscape.

Journal Article↗

PubMed1999

Continuous phase transition in a spin-glass model without time-reversal symmetry.

We investigate the phase transition in a strongly disordered short-range three-spin interaction model characterized by the absence of time-reversal symmetry in the Hamiltonian. In the mean-field limit the model is well described by the Adam-Gibbs-DiMarzio scenario for the glass transition; however, in the short-range case this picture turns out to be modified. The model presents a finite temperature continuous phase transition characterized by a divergent spin-glass susceptibility and a negative specific-heat exponent. We expect the nature of the transition in this three-spin model to be the same as the transition in the Edwards-Anderson model in a magnetic field, with the advantage that the strong crossover effects present in the latter case are absent.

Journal Article↗

PubMed1996