Influence of the Quantum Capacitance on Electrolyte Conductivity through 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 remains debated. Here, we model the coupling between the CNT quantum capacitance and the classical electrolyte-filled pore one and study how electrolyte transport is modulated when a gate voltage is applied to the CNT. Our work shows that under certain conditions the quantum capacitance is lower than the pore one due to the finite quasi-1D CNT electronic density of states and therefore controls the CNT surface charge density that dictates the confined electrolyte conductivity. The dependence of the computed surface charge and conductivity on reservoir salt concentration and gate voltage is thus intimately related to the electronic properties of the CNT. This approach provides key insight into why metallic CNTs have larger experimentally measured conductivities than semiconducting ones.

Impact of Single-Walled Carbon Nanotube Functionalization on Ion and Water Molecule Transport at the Nanoscale.

Nanofluidics has a very promising future owing to its numerous applications in many domains. It remains, however, very difficult to understand the basic physico-chemical principles that control the behavior of solvents confined in nanometric channels. Here, water and ion transport in carbon nanotubes is investigated using classical force field molecular dynamics simulations. By combining one single walled carbon nanotube (uniformly charged or not) with two perforated graphene sheets, we mimic single nanopore devices similar to experimental ones. The graphitic edges delimit two reservoirs of water and ions in the simulation cell from which a voltage is imposed through the application of an external electric field. By analyzing the evolution of the electrolyte conductivity, the role of the carbon nanotube geometric parameters (radius and chirality) and of the functionalization of the carbon nanotube entrances with OH or COO- groups is investigated for different concentrations of group functions.

Protein overexpression can induce the elongation of cell membrane nanodomains.

In cell membranes, proteins and lipids are organized into submicrometric nanodomains of varying sizes, shapes, and compositions, 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 mesopatterning mechanism is of relevance in several soft-matter systems because it relies on generic physical arguments.

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 versus R and the bulk electrolyte concentration ρ_{b}. We show how the ionic LV transition, directly induced by the abrupt change of the dielectric contribution of the PMF with κ, is favored by the Born self-energy and explore the decrease of the concentration in the pore with ε both in the vapor and liquid states. Phase diagrams 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 as a function of R. For charged nanopores, these exclusion effects compete with the electrostatic attraction that imposes the entry of counterions into the pore to enforce electroneutrality. 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.

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 is thoroughly explored. Our numerical results quantitatively agree with the previous analytical results obtained by Gueguen et al. [Eur. Phys. J. E 37, 76 (2014)] 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.

Dynamical control of denaturation bubble nucleation in supercoiled DNA minicircles.

We examine the behavior of supercoiled DNA minicircles containing between 200 and 400 base-pairs, also named microDNA, in which supercoiling favors thermally assisted DNA denaturation bubbles of nanometer size and controls their lifetime. Mesoscopic modeling and accelerated dynamics simulations allow us to overcome the limitations of atomistic simulations encountered in such systems, and offer detailed insight into the thermodynamic and dynamical properties associated with the nucleation and closure mechanisms of long-lived thermally assisted denaturation bubbles which do not stem from bending- or torque-driven stress. Suitable tuning of the degree of supercoiling and size of specifically designed microDNA is observed to lead to the control of opening characteristic times in the millisecond range, and closure characteristic times ranging over well distinct timescales, from microseconds to several minutes. We discuss how our results can be seen as a dynamical bandwidth which might enhance selectivity for specific DNA binding proteins.

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.

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 the presence of monovalent (Li^{+}, Na^{+}, K^{+}) and divalent (Mg^{2+}, Ca^{2+}) metallic and alkyl ammonium ions, over a large range 0.5 mM≤I≤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 nonlinear 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.

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.

Role of charge regulation and flow slip in the ionic conductance of nanopores: An analytical approach.

The number of precise conductance measurements in nanopores is quickly growing. 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 pH and salt concentration c_{s} using a simple charge regulation model, and (iv) a fixed surface charge density that is unaffected by pH 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}.

Energy required to pinch a DNA plectoneme.

DNA supercoiling plays an important role from a biological point of view. One of its consequences at the supramolecular 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_{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.

The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse.

T lymphocyte cytotoxicity relies on a synaptic ring of lymphocyte function-associated antigen 1 (LFA-1), which permits polarized delivery of lytic granules. How LFA-1 organization is controlled by underlying actin cytoskeleton dynamics is poorly understood. Here, we explored the contribution of the actin cytoskeleton regulator WASP to the topography of LFA-1 using a combination of microscopy modalities. We uncover that the reduced cytotoxicity of Wiskott-Aldrich syndrome patient-derived CD8+ T lymphocytes lacking WASP is associated with reduced LFA-1 activation, unstable synapse, and delayed lethal hit. At the nanometric scale, WASP constrains high-affinity LFA-1 into dense nanoclusters located in actin meshwork interstices. At the cellular scale, WASP is required for the assembly of a radial belt composed of hundreds of LFA-1 nanoclusters and for lytic granule docking within this belt. Our study unravels the nanoscale topography of LFA-1 at the lytic synapse and identifies WASP as a molecule controlling individual LFA-1 cluster density and LFA-1 nanocluster belt integrity.

How does temperature impact the conformation of single DNA molecules below melting temperature?

The double stranded DNA molecule undergoes drastic structural changes during biological processes such as transcription during which it opens locally under the action of RNA polymerases. Local spontaneous denaturation could contribute to this mechanism by promoting it. Supporting this idea, different biophysical studies have found an unexpected increase in the flexibility of DNA molecules with various sequences as a function of the temperature, which would be consistent with the formation of a growing number of locally denatured sequences. Here, we take advantage of our capacity to detect subtle changes occurring on DNA by using high throughput tethered particle motion to question the existence of bubbles in double stranded DNA under physiological salt conditions through their conformational impact on DNA molecules ranging from several hundreds to thousands of base pairs. Our results strikingly differ from previously published ones, as we do not detect any unexpected change in DNA flexibility below melting temperature. Instead, we measure a bending modulus that remains stable with temperature as expected for intact double stranded DNA.

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, which is introduced in the theory either as a Lagrange multiplier to conserve the total membrane area or as an external constraint. In this work we relate these two surface tensions both analytically and numerically. They are also compared to the Laplace tension γ, and the mechanical frame tension τ. Using the Helfrich model and one-loop renormalisation calculations, we obtain, in addition to the effective bending modulus κeff, a new expression for the effective surface tension σeff = σ - εkBT/(2ap) where kBT is the thermal energy, ap the projected cut-off area, and ε = 3 or 1 according to the allowed configurations that keep either the projected area or the total area constant. Moreover we show that the crumpling transition for an infinite planar membrane occurs for σeff = 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 within the Helfrich theory. As compared to alternative numerical models, no local constraint is applied and the shape is only controlled by the constant volume, the spontaneous curvature and σ. It is shown that the numerical fluctuation surface tension r is equal to σeff 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 [small sigma, Greek, circumflex]eff = σeffR2/κeff > 0 and a bending one for -1 < [small sigma, Greek, circumflex]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 [small sigma, Greek, circumflex]eff ≃ 0. We propose that the buckling transition, observed for planar supported membranes in the literature, occurs for [small sigma, Greek, circumflex]eff ≃ -1, the associated negative frame tension playing the role of a compressive force. Hence, a precise control of the value of σeff in simulations cannot but enhance our understanding of shape transitions of vesicles and cells.

Voltage-activated transport of ions through single-walled carbon nanotubes.

Ionic transport through single-walled carbon nanotubes (SWCNTs) is promising for many applications but remains both experimentally challenging and highly debated. Here we report ionic current measurements through microfluidic devices containing one or several SWCNTs of diameter of 1.2 to 2 nm unexpectedly showing a linear or a voltage-activated I-V dependence. Transition from an activated to a linear behavior, and stochastic fluctuations between different current levels were notably observed. For linear devices, the high conductance confirmed with different chloride salts indicates that the nanotube/water interface exhibits both a high surface charge density and flow slippage, in agreement with previous reports. In addition, the sublinear dependence of the conductance on the salt concentration points toward a charge-regulation mechanism. Theoretical modelling and computer simulations show that the voltage-activated behavior can be accounted for by the presence of local energy barriers along or at the ends of the nanotube. Raman spectroscopy reveals strain fluctuations along the tubes induced by the polymer matrix but displays insufficient doping or variations of doping to account for the apparent surface charge density and energy barriers revealed by ion transport measurements. Finally, experimental evidence points toward environment-sensitive chemical moieties at the nanotube mouths as being responsible for the energy barriers causing the activated transport of ions through SWCNTs within this diameter range.

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 also called protein clusters. The model includes a short-range attraction between proteins and a weaker long-range repulsion which ensures the existence of so-called cluster phases in equilibrium, where monomeric proteins coexist with finite-size domains. Our main finding is that, when taking recycling into account, the typical cluster size at steady state increases logarithmically with the recycling rate at fixed protein concentration. Using physically realistic model parameters, the predicted 2-fold increase due to recycling in living cells is most likely experimentally measurable with the help of super-resolution microscopy.

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."

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.

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 one to seven 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.

DNA denaturation bubbles: free-energy landscape and nucleation/closure rates.

The issue of the nucleation and slow closure mechanisms of non-superhelical stress-induced denaturation bubbles in DNA is tackled using coarse-grained MetaDynamics and Brownian simulations. A minimal mesoscopic model is used where the double helix is made of two interacting bead-spring rotating strands with a prescribed torsional modulus in the duplex state. We demonstrate that timescales for the nucleation (respectively, closure) of an approximately 10 base-pair bubble, in agreement with experiments, are associated with the crossing of a free-energy barrier of 22 kBT (respectively, 13 kBT) at room temperature T. MetaDynamics allows us to reconstruct accurately the free-energy landscape, to show that the free-energy barriers come from the difference in torsional energy between the bubble and duplex states, and thus to highlight the limiting step, a collective twisting, that controls the nucleation/closure mechanism, and to access opening time scales on the millisecond range. Contrary to small breathing bubbles, those more than 4 base-pair bubbles are of biological relevance, for example, when a pre-existing state of denaturation is required by specific DNA-binding proteins.