arXiv subjects

Manoel Manghi

Publications and source records attributed to Manoel Manghi.

At least 19 recordsLinked to original sources

arXiv2024

There and back again: bridging meso- and nanoscales to understand lipid vesicle patterning

We describe a complete methodology to bridge the scales between nanoscale Molecular Dynamics and (micrometer) mesoscale Monte Carlo simulations in lipid membranes and vesicles undergoing phase separation, in which curving molecular species are furthermore embedded. To go from the molecular to the mesoscale, we notably appeal to physical renormalization arguments enabling us to rigorously infer the mesoscale interaction parameters from its molecular counterpart. We also explain how to deal with the physical timescales at stake at the mesoscale. Simulating the so-obtained mesoscale system enables us to equilibrate the long wavelengths of the vesicles of interest, up to the vesicle size. Conversely, we then backmap from the meso- to the nano- scale, which enables us to equilibrate in turn the short wavelengths down to the molecular length-scales. By applying our approach to the specific situation of the patterning of a vesicle membrane, we show that macroscopic membranes can thus be equilibrated at all length-scales in achievable computational time offering an original strategy to address the fundamental challenge of time scale in simulations of large bio-membrane systems.

cond-mat.soft↗

arXiv2023

Quantum capacitance governs electrolyte conductivity in carbon nanotubes

In recent experiments, unprecedentedly large values for the conductivity of electrolytes through carbon nanotubes (CNTs) have been measured, possibly owing to flow slip and a high pore surface charge density whose origin is still unknown. By accounting for the coupling between the {quantum} CNT and the {classical} electrolyte-filled pore capacitances, we study the case where a gate voltage is applied to the CNT. The computed surface charge and conductivity dependence on reservoir salt concentration and gate voltage are intimately connected to the CNT electronic density of states. This approach provides key insight into why metallic CNTs have larger conductivities than semi-conducting ones.

cond-mat.soft↗

arXiv2023

dsDNA persistence length with divalent ions

Finding a theoretical formula for the persistence length of polyelectrolytes for the whole experimental range of salt concentration is a long standing challenge. Using the Tethered Particle Motion technique, the double-stranded DNA persistence length is measured for four monovalent and divalent salts on a three-decade concentration range. The formula proposed by Trizac and Shen [EPL, 116 18007 (2016)] and extended to divalent ions fits the data. This formula mixes the high salt limit solution of the Poisson-Boltzmann equation together with the DNA charge renormalisation. Magnesium ions induce a fitted DNA radius smaller than the geometrical one, consistent with a site-specific binding.

cond-mat.soft↗

arXiv2022

Protein over-expression can induce the elongation of cell membrane nanodomains

In cell membranes, proteins and lipids are organized into sub-micrometric nanodomains of varying size, shape and composition, performing specific functions. Despite their biological importance, the detailed morphology of these nanodomains remains unknown. Not only can they hardly be observed by conventional microscopy due to their small size, but there is no full consensus on the theoretical models to describe their structuring and their shapes. Here, we use a combination of analytical calculations and Monte Carlo simulations based upon a model coupling membrane composition and shape to show that increasing protein concentration leads to an elongation of membrane nanodomains. The results are corroborated by Single Particle Tracking measurements on HIV receptors, whose level of expression in the membrane of specifically designed living cells can be tuned. These findings highlight that protein abundance can modulate nanodomain shape and potentially their biological function. Beyond biomembranes, this meso-patterning mechanism is of relevance in several soft-matter systems because it relies on generic physical arguments.

physics.bio-ph↗

arXiv2021

Competition between Born solvation, dielectric exclusion, and Coulomb attraction in spherical nanopores

The recent measurement of a very low dielectric constant, $ε$, of water confined in nanometric slit pores leads us to reconsider the physical basis of ion partitioning into nanopores. For confined ions in chemical equilibrium with a bulk of dielectric constant $ε_b>ε$, three physical mechanisms, at the origin of ion exclusion in nanopores, are expected to be modified due to this dielectric mismatch: dielectric exclusion at the water-pore interface (with membrane dielectric constant, $ε_m<ε$), the solvation energy related to the difference in Debye-Hückel screening parameters in the pore, $κ$, and in the bulk $κ_b$, and the classical Born solvation self-energy proportional to $ε^{-1}-ε_b^{-1}$. Our goal is to clarify the interplay between these three mechanisms and investigate the role played by the Born contribution in ionic liquid-vapor (LV) phase separation in confined geometries. We first compute analytically the potential of mean force (PMF) of an ion of radius $R_i$ located at the center of a nanometric spherical pore of radius $R$. Computing the variational grand potential for a solution of confined ions, we then deduce the partition coefficients of ions in the pore. Phase diagrams of the LV transition are established for various parameter values and we show that a signature of this phase transition can be detected by monitoring the total osmotic pressure. For charged nanopores, these exclusion effects compete with the electrostatic attraction that imposes the entry of counterions into the pore to enforce electro-neutrality. This study will therefore help in deciphering the respective roles of the Born self-energy and dielectric mismatch in experiments and simulations of ionic transport through nanopores.

cond-mat.soft↗

arXiv2020

Domain formation in bicomponent vesicles induced by composition-curvature coupling

Lipid vesicles composed of a mixture of two types of lipids are studied by intensive Monte-Carlo numerical simulations. The coupling between the local composition and the membrane shape is induced by two different spontaneous curvatures of the components. We explore the various morphologies of these biphasic vesicles coupled to the observed patterns such as nano-domains or labyrinthine mesophases. The effect of the difference in curvatures, the surface tension and the interaction parameter between components are thoroughly explored. Our numerical results quantitatively agree with previous analytical results obtained by [Gueguen et al., Eur. Phys. J. E, 2014, vol. 37, p. 76] in the disordered (high temperature) phase. Numerical simulations allow us to explore the full parameter space, especially close to and below the critical temperature, where analytical results are not accessible. Phase diagrams are constructed and domain morphologies are quantitatively studied by computing the structure factor and the domain size distribution. This mechanism likely explains the existence of nano-domains in cell membranes as observed by super-resolution fluorescence microscopy.

cond-mat.soft↗

arXiv2019

Statistical physics and mesoscopic modeling to interpret tethered particle motion experiments

Tethered particle motion experiments are versatile single-molecule techniques enabling one to address in vitro the molecular properties of DNA and its interactions with various partners involved in genetic regulations. These techniques provide raw data such as the tracked particle amplitude of movement, from which relevant information about DNA conformations or states must be recovered. Solving this inverse problem appeals to specific theoretical tools that have been designed in the two last decades, together with the data pre-processing procedures that ought to be implemented to avoid biases inherent to these experimental techniques. These statistical tools and models are reviewed in this paper.

physics.bio-ph↗

arXiv2018

Dependence of DNA persistence length on ionic strength and ion type

Even though the persistence length $L_P$ of double-stranded DNA plays a pivotal role in cell biology and nanotechnologies, its dependence on ionic strength $I$ lacks a consensual description. Using a high-throughput single-molecule technique and statistical physics modeling, we measure $L_P$ in presence of monovalent (Li$^+$, Na$^+$, K$^+$) and divalent (Mg$^{2+}$, Ca$^{2+}$) metallic and alkyl ammonium ions, over a large range 0.5 mM $\leq I\leq 5$ M. We show that linear Debye-Hückel-type theories do not describe even part of these data. By contrast, the Netz-Orland and Trizac-Shen formulas, two approximate theories including non-linear electrostatic effects and the finite DNA radius, fit our data with divalent and monovalent ions, respectively, over the whole $I$ range. Furthermore the metallic ion type does not influence $L_P(I)$, in contrast to alkyl ammonium monovalent ions at high $I$.

physics.bio-ph↗

arXiv2018

A rationale for mesoscopic domain formation in biomembranes

Cell plasma membranes display a dramatically rich structural complexity characterized by functional sub-wavelength domains with specific lipid and protein composition. Under favorable experimental conditions, patterned morphologies can also be observed in vitro on model systems such as supported membranes or lipid vesicles. Lipid mixtures separating in liquid-ordered and liquid-disordered phases below a demixing temperature play a pivotal role in this context. Protein-protein and protein-lipid interactions also contribute to membrane shaping by promoting small domains or clusters. Such phase separations displaying characteristic length-scales falling in-between the nanoscopic, molecular scale on the one hand and the macroscopic scale on the other hand, are named mesophases in soft condensed matter physics. In this review, we propose a classification of the diverse mechanisms leading to mesophase separation in biomembranes. We distinguish between mechanisms relying upon equilibrium thermodynamics and those involving out-of-equilibrium mechanisms, notably active membrane recycling. In equilibrium, we especially focus on the many mechanisms that dwell on an up-down symmetry breaking between the upper and lower bilayer leaflets. Symmetry breaking is an ubiquitous mechanism in condensed matter physics at the heart of several important phenomena. In the present case, it can be either spontaneous (domain buckling) or explicit, i.e., due to an external cause (global or local vesicle bending properties). Whenever possible, theoretical predictions and simulation results are confronted to experiments on model systems or living cells, which enables us to identify the most realistic mechanisms from a biological perspective.

cond-mat.soft↗

arXiv2018

Role of charge regulation and flow slip on the ionic conductance of nanopores: an analytical approach

The number of precise conductance measurements in nanopores is quickly growing. In order to clarify the dominant mechanisms at play and facilitate the characterization of such systems for which there is still no clear consensus, we propose an analytical approach to the ionic conductance in nanopores that takes into account (i) electro-osmotic effects, (ii) flow slip at the pore surface for hydrophobic nanopores, (iii) a component of the surface charge density that is modulated by the reservoir $p$H and salt concentration $c_s$ using a simple charge regulation model, and (iv) a fixed surface charge density that is unaffected by $p$H and $c_s$. Limiting cases are explored for various ranges of salt concentration and our formula is used to fit conductance experiments found in the literature for carbon nanotubes. This approach permits us to catalog the different possible transport regimes and propose an explanation for the wide variety of currently known experimental behavior for the conductance versus $c_s$.

cond-mat.soft↗

arXiv2018

Control of DNA denaturation bubble nucleation to advance nano-biosensing

In the demanding biosensing environment, improving selection efficiency strategies has become an issue of great significance. DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, are representative of the supercoiled DNA loops found in nature. Their short size makes them extremely susceptible to writhe and twist, which is known to play a central role in DNA denaturation. We investigate minicircle lengths and superhelical densities that induce DNA denaturation bubbles of nanometer size and control well-defined long-life. Mesoscopic modeling and accelerated dynamics simulations allow us to study accurately the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived denaturation bubbles. Our results pave the way for new types of DNA biosensors with enhanced selectivity for specific DNA binding proteins.

physics.bio-ph↗

arXiv2018

Energy required to pinch a DNA plectoneme

DNA supercoiling plays an important role on a biological point of view. One of its consequences at the supra-molecular level is the formation of DNA superhelices named plectonemes. Normally separated by a distance on the order of 10 nm, the two opposite double-strands of a DNA plectoneme must be brought closer if a protein or protein complex implicated in genetic regulation is to be bound simultaneously to both strands, as if the plectoneme was locally pinched. We propose an analytic calculation of the energetic barrier, of elastic nature, required to bring closer the two loci situated on the opposed double-strands. We examine how this energy barrier scales with the DNA supercoiling. For physically relevant values of elastic parameters and of supercoiling density, we show that the energy barrier is in the $k_{\rm B} T$ range under physiological conditions, thus demonstrating that the limiting step to loci encounter is more likely the preceding plectoneme slithering bringing the two loci side by side.

cond-mat.soft↗

arXiv2017

Fluctuation tension and shape transition of vesicles: renormalisation calculations and Monte Carlo simulations

It has been known for long that the fluctuation surface tension of membranes $r$, computed from the height fluctuation spectrum, is not equal to the bare surface tension $σ$ introduced in the Helfrich theory. In this work we relate these two surface tensions both analytically and numerically and compare them to the Laplace tension $γ$, and the mechanical frame tension $τ$. Using one-loop renormalisation calculations, we obtain, in addition to the effective bending modulus $κ_{\rm eff}$, a new expression for the effective surface tension $σ_{\rm eff}=σ- εk_{\rm B}T/(2a_p)$ where $a_p$ the projected cut-off area, and $ε=3$ or 1 according to the allowed configurations. Moreover we show that the crumpling transition for an infinite planar membrane occurs for $σ_{\rm eff}=0$, and also that it coincides with vanishing Laplace and frame tensions. Using extensive Monte Carlo (MC) simulations, triangulated membranes of vesicles made of $N=100-2500$ vertices are simulated. No local constraint is applied. It is shown that the numerical $r$ is equal to $σ_{\rm eff}$ both with radial MC moves ($ε=3$) and with corrected MC moves locally normal to the fluctuating membrane ($ε=1$). For finite vesicles of typical size $R$, two different regimes are defined: a tension regime for $\hat σ_{\rm eff}=σ_{\rm eff}R^2/κ_{\rm eff}>0$ and a bending one for $-1<\hat σ_{\rm eff}<0$. A shape transition from a quasi-spherical shape imposed by the large surface energy, to more deformed shapes only controlled by the bending energy, is observed numerically at $\hat σ_{\rm eff}\simeq 0$. We propose that the buckling transition, observed for planar supported membranes in the literature, occurs for $\hat σ_{\rm eff}\simeq-1$, the associated negative frame tension playing the role of a compressive force.

cond-mat.soft↗

arXiv2016

Physics of base-pairing dynamics in DNA

As a key molecule of Life, Deoxyribonucleic acid (DNA) is the focus of numbers of investigations with the help of biological, chemical and physical techniques. From a physical point of view, both experimental and theoretical works have brought quantitative insights into DNA base-pairing dynamics that we review in this Report, putting emphasis on theoretical developments. We discuss the dynamics at the base-pair scale and its pivotal coupling with the polymer one, with a polymerization index running from a few nucleotides to tens of kilo-bases. This includes opening and closure of short hairpins and oligomers as well as zipping and unwinding of long macromolecules. We review how different physical mechanisms are either used by Nature or utilized in biotechnological processes to separate the two intertwined DNA strands, by insisting on quantitative results. They go from thermally-assisted denaturation bubble nucleation to force- or torque- driven mechanisms. We show that the helical character of the molecule, possibly supercoiled, can play a key role in many denaturation and renaturation processes. We categorize the mechanisms according to the relative timescales associated with base-pairing and chain degrees of freedom such as bending and torsional elastic ones. In some specific situations, these chain degrees of freedom can be integrated out, and the quasi- static approximation is valid. The complex dynamics then reduces to the diffusion in a low-dimensional free-energy landscape. In contrast, some important cases of experimental interest necessarily appeal to far-from-equilibrium statistical mechanics and hydrodynamics.

cond-mat.soft↗

arXiv2016

A variational approach to the liquid-vapor phase transition for hardcore ions in the bulk and in nanopores

We employ a field-theoretical variational approach to study the behavior of ionic solutions in the grand canonical ensemble. To describe properly the hardcore interactions between ions, we use a cutoff in Fourier space for the electrostatic contribution of the grand potential and the Carnahan-Starling equation of state with a modified chemical potential for the pressure one. We first calibrate our method by comparing its predictions at room temperature with Monte Carlo results for excess chemical potential and energy. We then validate our approach in the bulk phase by describing the classical "ionic liquid-vapor" phase transition induced by ionic correlations at low temperature, before applying it to electrolytes at room temperature confined to nanopores embedded in a low dielectric medium and coupled to an external reservoir of ions. The ionic concentration in the nanopore is then correctly described from very low bulk concentrations, where dielectric exclusion shifts the transition up to room temperature for sufficiently tight nanopores, to high concentrations where hardcore interactions dominate which, as expected, modify only slightly this ionic "capillary evaporation".

cond-mat.soft↗

arXiv2016

Nanodomains in biomembranes with recycling

Cell membranes are out of thermodynamic equilibrium notably because of membrane recycling, i.e. active exchange of material with the cytosol. We propose an analytically tractable model of biomembrane predicting the effects of recycling on the size of protein nanodomains. It includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of so-called cluster phases at equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that when taking recycling into account, the typical cluster size increases logarithmically with the recycling rate. Using physically realistic model parameters, the predicted two-fold increase due to recycling in living cells is very likely experimentally measurable with the help of super-resolution microscopy.

cond-mat.soft↗

arXiv2015

Ionic transport through sub-10 nm diameter hydrophobic high-aspect ratio nanopores: experiment, theory and simulation

Fundamental understanding of ionic transport at the nanoscale is essential for developing biosensors based on nanopore technology and new generation high-performance nanofiltration membranes for separation and purification applications. We study here ionic transport through single putatively neutral hydrophobic nanopores with high aspect ratio (of length L=6 μm with diameters ranging from 1 to 10 nm) and with a well controlled cylindrical geometry. We develop a detailed hybrid mesoscopic theoretical approach for the electrolyte conductivity inside nanopores, which considers explicitly ion advection by electro-osmotic flow and possible flow slip at the pore surface. By fitting the experimental conductance data we show that for nanopore diameters greater than 4 nm a constant weak surface charge density of about 10$^{-2}$ C m$^{-2}$ needs to be incorporated in the model to account for conductance plateaus of a few pico-Siemens at low salt concentrations. For tighter nanopores, our analysis leads to a higher surface charge density, which can be attributed to a modification of ion solvation structure close to the pore surface, as observed in the molecular dynamics simulations we performed.

cond-mat.mes-hall↗

arXiv2015

Probing a label-free local bend in DNA by single-molecule Tethered Particle Motion

Being capable of characterizing DNA local bending is essential to understand thoroughly many biological processes because they involve a local bending of the double helix axis, either intrinsic to the sequence or induced by the binding of proteins. Developing a method to measure DNA bend angles that does not perturb the conformation of the DNA itself or the DNA-protein complex is a challenging task. Here, we propose a joint theory-experiment high throughput approach to rigorously measure such bend angles using the Tethered Particle Motion (TPM) technique. By carefully modeling the TPM geometry, we propose a simple formula based on a kinked Worm-Like Chain model to extract the bend angle from TPM measurements. Using constructs made of 575 base-pair DNAs with in-phase assemblies of 1 to 7 6A-tracts, we find that the sequence CA6CGG induces a bend angle of 19 [4] °. Our method is successfully compared to more theoretically complex or experimentally invasive ones such as cyclization, NMR, FRET or AFM. We further apply our procedure to TPM measurements from the literature and demonstrate that the angles of bends induced by proteins, such as Integration Host Factor (IHF) can be reliably evaluated as well.

q-bio.BM↗