arXiv subjects

Fernando Falo

Publications and source records attributed to Fernando Falo.

At least 19 recordsLinked to original sources

arXiv2023

Polymer translocation driven by longitudinal and transversal time-dependent end-pulling forces

Polymer translocation has long been a topic of interest in the field of biological physics given its relevance in both biological (protein and DNA/RNA translocation through nuclear and cell membranes) and technological processes (nanopore DNA sequencing, drug delivery). In this work, we simulate the translocation of a semiflexible homopolymer through an extended pore, driven by both a constant and a time-dependent end-pulled force, employing a model introduced in previous studies. The time dependence is simplistically modeled as a cosine function, and we distinguish between two scenarios for the driving -- longitudinal force and transversal force -- depending on the relative orientation of the force, parallel or perpendicular respectively, with respect to the pore axis. Beside some key differences between the two drivings, the mean translocation times present a large minimum region as function of the frequency of the force that is typical of the Resonant Activation effect. The presence of the minimum is independent on the elastic characteristics of the polymeric chains and reveals a linear relation between the optimum mean translocation time and the corresponding period of the driving. The mean translocation times show different scaling exponent with the polymer length for different flexibilities. Lastly, we derive an analytical expression of the mean translocation time for low driving frequency, which clearly agrees with the simulations.

cond-mat.soft↗

arXiv2022

Elastic traits of the extensible discrete wormlike chain model

Polymer models play the special role of elucidating the elementary features describing the physics of long molecules and become essential to interpret the measurements of their magnitudes. In this work the end-to-end distance of an extensible discrete worm-like chain polymer as a function of the applied force has been calculated both numerically and analytically, the latter as an effective approximation. The numerical evaluation uses the Transfer Matrix formalism to obtain an exact calculation of the partition function, while the analytic derivations generalize the simple phenomenological formulas largely used up to now. The obtained formulas are simple enough to be implemented in the fit analysis of experimental data of semi-flexible extensible polymers, with the result that the elastic parameters obtained are compatible with previous measurements, and more, their accuracy strongly improves in a large range of chain extensibility.

cond-mat.soft↗

arXiv2018

Force spectroscopy analysis in polymer translocation

This paper reports the force spectroscopy analysis of a polymer that translocates from one side of a membrane to the other side through an extended pore, pulled by a cantilever that moves with constant velocity against the damping and the potential barrier generated by the reaction of the membrane walls. The polymer is modeled as a beads-springs chain with both excluded volume and bending contributions, and moves in a stochastic three dimensional environment described by a Langevin dynamics at fixed temperature. The force trajectories recorded at different velocities reveal two unexplored exponential regimes: the force increases when the first part of the chain enters the pore, and then decreases when the first monomer reaches the trans region. The spectroscopy analysis of the force values permit the estimation of the free energy barrier as well as the limit force to permit the translocation. The stall force to maintain the polymer fixed has been also calculated independently, and its value confirms the force spectroscopy outcomes.

cond-mat.soft↗

arXiv2018

Analytical results of the extensible freely jointed chain model

Based on classical statistical mechanics, we calculate analytically the length extension and the fluctuations, under a pulling force, of a polymer modelled as a freely jointed chain with extensible bonds, the latter considered as harmonic springs. We obtain an analytical formula for the partition function, and derive both the extension curve of the chain and the fluctuations as a function of the force. An independent high force approximation has been also evaluated. The analytical formulas have been validated by analysing the exactness of their fit on data obtained from Langevin simulations, and compared with the phenomenological expressions largely used in the past literature.

cond-mat.stat-mech↗

arXiv2015

Mechanical Unfolding of a Simple Model Protein Goes Beyond the Reach of One-Dimensional Descriptions

We study the mechanical unfolding of a simple model protein. The Langevin dynamics results are analyzed using Markov-model methods which allow to describe completely the configurational space of the system. Using transition path theory we also provide a quantitative description of the unfolding pathways followed by the system. Our study shows a complex dynamical scenario. In particular, we see that the usual one-dimensional picture: free-energy vs end-to-end distance representation, gives a misleading description of the process. Unfolding can occur following different pathways and configurations which seem to play a central role in one-dimensional pictures are not the intermediate states of the unfolding dynamics.

physics.bio-ph↗

arXiv2014

An integrative approach for modeling and simulation of Heterocyst pattern formation in Cyanobacteria strands

A comprehensive approach to cellular differentiation in cyanobacteria is developed. To this aim, the process of heterocyst cell formation is studied under a systems biology point of view. By relying on statistical physics techniques, we translate the essential ingredients and mechanisms of the genetic circuit into a set of differential equations that describes the continuous time evolution of combined nitrogen, PatS, HetR and NtcA concentrations. The detailed analysis of these equations gives insight into the single cell dynamics. On the other hand, the inclusion of diffusion and noisy conditions allows simulating the formation of heterocysts patterns in cyanobacteria strains. The time evolution of relevant component concentrations are calculated allowing for a comparison with experiments. Finally, we discuss the validity and the possible improvements of the model.

q-bio.CB↗

arXiv2013

Modeling the interaction of DNA with alternating fields

We study the influence of a THz field on thermal properties of DNA molecules. A Peyrard- Bishop-Dauxois model with the inclusion of a solvent interaction term is considered. The THz field is included as a sinusoidal driven force in the equation of mo tion. We show how under certain field and system parameters, melting transition and bubble formation are modified.

physics.bio-ph↗

arXiv2012

Directional motion of forced polymer chains with hydrodynamic interaction

We study the propulsion of a one-dimensional (1D) polymer chain under sinusoidal external forces in the overdamped (low Reynolds number) regime. We show that, when hydrodynamical interactions are included, the polymer presents directional motion which depends on the phase differences of the external force applied along the chain. Moreover, the velocity shows a maximum as a function of the frequency. We discuss the relevance of all these results in light of recent nanotechnology experiments.

cond-mat.soft↗

arXiv2012

Translocation of a polymer chain driven by a dichotomous noise

We consider the translocation of a one-dimensional polymer through a pore channel helped by a motor driven by a dichotomous noise with time exponential correlation. We are interested in the study of the translocation time, mean velocity and stall force of the system as a function of the mean driving frequency. We find a monotonous translocation time, in contrast with the mean velocity which shows a pronounced maximum at a given frequency. Interestingly, the stall force shows a nonmonotonic behavior with the presence of a minimum. The influence of the spring elastic constant to the mean translocation times and velocities is also presented.

cond-mat.soft↗

arXiv2012

Michaelis-Menten dynamics of a polymer chain out of a dichotomous ATP-based motor

We present a model of an ATP-fueled molecular machine which push a polymer through a pore channel. The machine acts between two levels (working-waiting), and the working one remains active for a fixed time giving a constant force. The machine activation rate can be put in relationship with the available ATP concentration in the solution, which gives the necessary energy supply. The translocation time shows a monotonic behavior as a function of the activation frequency and the velocity follows a Michaelis-Menten law that arises naturally in this description. The estimation of the stall force of the motor follows a corrected Michaelis-Menten law which still is to be checked in experimental investigation. The results presented agree with recent biological experimental findings.

cond-mat.soft↗

arXiv2011

Tug-of-war of molecular motors: the effects of uneven load sharing

We analyze theoretically the problem of cargo transport along microtubules by motors of two species with opposite polarities. We consider two different one-dimensional models previously developed in the literature. On the one hand, a quite widespread model which assumes equal force sharing, here referred to as mean field model (MFM). On the other hand, a stochastic model (SM) which considers individual motor-cargo links. We find that in generic situations the MFM predicts larger cargo mean velocity, smaller mean run time and less frequent reversions than the SM. These phenomena are found to be consequences of the load sharing assumptions and can be interpreted in terms the probabilities of the different motility states. We also explore the influence of the viscosity in both models and the role of the stiffness of the motor-cargo links within the SM. Our results show that the mean cargo velocity is independent of the stiffness while the mean run time decreases with such a parameter. We explore the case of symmetric forward and backward motors considering kinesin- 1 parameters, and the problem of transport by kinesin-1 and cytoplasmic dyneins considering two different sets of parameters previously proposed for dyneins.

physics.bio-ph↗

arXiv2010

Influence of direct motor-motor interaction in models for cargo transport by a single team of motors

We analyze theoretically the effects of excluded-volume interactions between motors on the dynamics of a cargo driven by multiple motors. The model considered shares many commons with other recently proposed in the literature, with the addition of direct interaction between motors and motor back steps. The cargo is assumed to follow a continuum Langevin dynamics, while individual motors evolve following a Monte Carlo algorithm based on experimentally accessible probabilities for discrete forward and backward jumps, and attachment and detachment rates. The links between cargo and motors are considered as non linear springs. By means of numerical simulations we compute the relevant quantities characterizing the dynamical properties of the system, and we compare the results to those for non interacting motors. We find that interactions lead to quite relevant changes in the force-velocity relation for cargo, with a considerable reduction of the stall force, and cause also a notable decrease of the run length. These effects are mainly due to traffic-like phenomena in the microtubule. The consideration of several parallel tracks for motors reduces such effects. However, we find that for realistic values of the number of motors and the number of tracks, the influence of interactions on the global parameters of transport of cargo are far from being negligible. Our studies provide also an analysis of the relevance of motor back steps on the modeling, and of the influence of different assumptions for the detachment rates. In particular, we discuss these two aspects in connection with the possibility of observing processive back motion of cargo at large load forces.

physics.bio-ph↗

arXiv2010

Translocation time of periodically forced polymer chains

We show the presence of both a minimum and clear oscillations in the frequency dependence of the translocation time of a polymer described as a unidimensional Rouse chain driven by a spatially localized oscillating linear potential. The observed oscillations of the mean translocation time arise from the synchronization between the very mean translocation time and the period of the external force. We have checked the robustness of the frequency value for the minimum translocation time by changing the damping parameter, finding a very simple relationship between this frequency and the correspondent translocation time. The translocation time as a function of the polymer length has been also evaluated, finding a precise $L^2$ scaling. Furthermore, the role played by the thermal fluctuations described as a Gaussian uncorrelated noise has been also investigated, and the analogies with the resonant activation phenomenon are commented.

cond-mat.soft↗

arXiv2010

Thermal and mechanical properties of a DNA model with solvation barrier

We study the thermal and mechanical behavior of DNA denaturation in the frame of the mesoscopic Peyrard- Bishop-Dauxois model with the inclusion of solvent interaction. By analyzing the melting transition of a homogeneous A-T sequence, we are able to set suitable values of the parameters of the model and study the formation and stability of bubbles in the system. Then, we focus on the case of the P5 promoter sequence and use the Principal Component Analysis of the trajectories to extract the main information on the dynamical behavior of the system. We find that this analysis method gives an excellent agreement with previous biological results.

physics.bio-ph↗

arXiv2009

Exploring the Free Energy Landscape: From Dynamics to Networks and Back

The knowledge of the Free Energy Landscape topology is the essential key to understand many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers are, how the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are. Exploring the landscape by molecular dynamics simulations, the microscopic data of the trajectory are encoded into a Conformational Markov Network. The structure of this graph reveals the regions of the conformational space corresponding to the basins of attraction. In addition, handling the Conformational Markov Network, relevant kinetic magnitudes as dwell times or rate constants, and the hierarchical relationship among basins, complete the global picture of the landscape. We show the power of the analysis studying a toy model of a funnel-like potential and computing efficiently the conformers of a short peptide, the dialanine, paving the way to a systematic study of the Free Energy Landscape in large peptides.

q-bio.BM↗

arXiv2008

A model for hand-over-hand motion of molecular motors

A simple flashing ratchet model in two dimensions is proposed to simulate the hand-over-hand motion of two head molecular motors like kinesin. Extensive Langevin simulations of the model are performed. Good qualitative agreement with the expected behavior is observed. We discuss different regimes of motion and efficiency depending of model parameters.

physics.bio-ph↗

arXiv2004

A double-deletion method to quantifying incremental binding energies in proteins from experiment. Example of a destabilizing hydrogen bonding pair

The contribution of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory, experiment and simulation. Although hydrogen bonds are major determinants of protein structure and function, their contribution to protein stability is still unclear and widely debated. The best method so far devised to estimate the contribution of side-chain interactions to protein stability is double-mutant-cycle analysis, but the interaction energies so derived are not identical to incremental binding energies (the energies quantifying net contributions of two interacting groups to protein stability). Here we introduce double-deletion analysis of isolated residue pairs as a means to precisely quantify incremental binding. The method is exemplified by studying a surface-exposed hydrogen bond in a model protein (Asp96/Asn128 in apoflavodoxin). Combined substitution of these residues by alanines slightly destabilizes the protein, due to a decrease in hydrophobic surface burial. Subtraction of this effect, however, clearly indicates that the hydrogen-bonded groups in fact destabilize the native conformation. In addition, Molecular Dynamics simulations and classic double-mutant-cycle analysis explain quantitatively that, due to frustration, the hydrogen bond must form in the native structure because, when the two groups get approximated upon folding their binding becomes favorable. We would like to remark two facts: that this is the first time the contribution of a specific hydrogen bond to protein stability has been measured from experiment, and that more hydrogen bonds need to be analyzed in order to draw general conclusions on protein hydrogen bonds energetics. To that end, the double deletion method should be of help.

q-bio.BM↗

arXiv1999

Ratchet potential for fluxons in Josephson-Junction arrays

We propose a simple configuration of a one-dimensional parallel array of Josephson junctions in which the pinning potential for trapped fluxons lacks inversion symmetry (ratchet potential). This sytem can be modelised by a set of non-linear pendula with alternating lengths and harmonic couplings. We show, by molecular dynamics simulations, that fluxons behave as single particles in which the predictions for overdamped thermal ratchet can be easily verified.

cond-mat↗