Javier Cervera

Ionic conduction, rectification, and selectivity in single conical nanopores

Modern track-etching methods allow the preparation of membranes containing a single charged conical nanopore that shows high ionic permselectivity due to the electrical interactions of the surface pore charges with the mobile ions in the aqueous solution. The nanopore has potential applications in electrically assisted single-particle detection, analysis, and separation of biomolecules. We present a detailed theoretical and experimental account of the effects of pore radii and electrolyte concentration on the current-voltage and current-concentration curves. The physical model used is based on the Nernst-Planck and Poisson equations. Since the validity of continuum models for the description of ion transport under different voltages and concentrations is recognized as one of the main issues in the modeling of future applications, special attention is paid to the fundamental understanding of the electrical interactions between the nanopore fixed charges and the mobile charges confined in the reduced volume of the inside solution.

Pore structure and function of synthetic nanopores with fixed charges: tip shape and rectification properties.

We present a complete theoretical study of the relationship between the structure (tip shape and dimensions) and function (selectivity and rectification) of asymmetric nanopores on the basis of previous experimental studies. The theoretical model uses a continuum approach based on the Nernst-Planck equations. According to our results, the nanopore transport properties, such as current-voltage (I-V) characteristics, conductance, rectification ratio, and selectivity, are dictated mainly by the shape of the pore tip (we have distinguished bullet-like, conical, trumpet-like, and hybrid shapes) and the concentration of pore surface charges. As a consequence, the nanopore performance in practical applications will depend not only on the base and tip openings but also on the pore shape. In particular, we show that the pore opening dimensions estimated from the pore conductance can be very different, depending on the pore shape assumed. The results obtained can also be of practical relevance for the design of nanopores, nanopipettes, and nanoelectrodes, where the electrical interactions between the charges attached to the nanostructure and the mobile charges confined in the reduced volume of the inside solution dictate the device performance in practical applications. Because single tracks are the elementary building blocks for nanoporous membranes, the understanding and control of their individual properties should also be crucial in protein separation, water desalination, and bio-molecule detection using arrays of identical nanopores.

Single Cigar-Shaped Nanopores Functionalized with Amphoteric Amino Acid Chains: Experimental and Theoretical Characterization

We present an experimental and theoretical characterization of single cigar-shaped nanopores with pH-responsive carboxylic acid and lysine chains functionalized on the pore surface. The nanopore characterization includes (i) optical images of the nanostructure obtained by FESEM; (ii) different chemical procedures for the nanopore preparation (etching time and functionalizations; pH and electrolyte concentration of the external solution) allowing externally tunable nanopore responses monitored by the current-voltage (I-V) curves; and (iii) transport simulations obtained with a multilayer nanopore model. We show that a single, approximately symmetric nanopore can be operated as a reconfigurable diode showing different rectifying behaviors by applying chemical and electrical signals. The remarkable characteristics of the new nanopore are the sharp response observed in the I-V curves, the improved tunability (with respect to previous designs of symmetric nanopores) which is achieved because of the direct external access to the nanostructure mouths, and the broad range of rectifying properties. The results concern both fundamental concepts useful for the understanding of transport processes in biological systems (ion channels) and applications relevant for tunable nanopore technology (information processing and drug controlled release).

Ion transport and selectivity in nanopores with spatially inhomogeneous fixed charge distributions.

Polymeric nanopores with fixed charges show ionic selectivity when immersed in aqueous electrolyte solutions. The understanding of the electrical interaction between these charges and the mobile ions confined in the inside nanopore solution is the key issue in the design of potential applications. The authors have theoretically described the effects that spatially inhomogeneous fixed charge distributions exert on the ionic transport and selectivity properties of the nanopore. A comprehensive set of one-dimensional distributions including the skin, core, cluster, and asymmetric cases are analyzed on the basis of the Nernst-Planck equations. Current-voltage curves, nanopore potentials, and transport numbers are calculated for the above distributions and compared with those obtained for a homogeneously charged nanopore with the same average fixed charge concentration. The authors have discussed if an appropriate design of the spatial fixed charge inhomogeneity can lead to an enhancement of the transport and selectivity with respect to the homogeneous nanopore case. Finally, they have compared the theoretical predictions with relevant experimental data.

Calcium binding and ionic conduction in single conical nanopores with polyacid chains: model and experiments.

Calcium binding to fixed charge groups confined over nanoscale regions is relevant to ion equilibrium and transport in the ionic channels of the cell membranes and artificial nanopores. We present an experimental and theoretical description of the dissociation equilibrium and transport in a single conical nanopore functionalized with pH-sensitive carboxylic acid groups and phosphonic acid chains. Different phenomena are simultaneously present in this basic problem of physical and biophysical chemistry: (i) the divalent nature of the phosphonic acid groups fixed to the pore walls and the influence of the pH and calcium on the reversible dissociation equilibrium of these groups; (ii) the asymmetry of the fixed charge density; and (iii) the effects of the applied potential difference and calcium concentration on the observed ionic currents. The significant difference between the carboxylate and phosphonate groups with respect to the calcium binding is clearly observed in the corresponding current-voltage (I-V) curves and can be rationalized by using a simple molecular model based on the grand partition function formalism of statistical thermodynamics. The I-V curves of the asymmetric nanopore can be described by the Poisson and Nernst-Planck equations. The results should be of interest for the basic understanding of divalent ion binding and transport in biological ion channels, desalination membranes, and controlled drug release devices.

Theoretical description of the ion transport across nanopores with titratable fixed charges: analogies between ion channels and synthetic pores.

Recently developed nanometer-sized synthetic pores display several properties so far believed to be distinctive features of a large variety of biological wide ion channels. Thus conductance in the pS-nS range, pH-dependent ion selectivity, fluctuations of current between open and closed states, flux inhibition caused by protons or divalent cations, current rectification, and the ability to perform selective macromolecule sizing and counting are found in synthetic and biological channels alike. Despite other differences such as pore size and geometry, the similarities open a new field for exploring specific technological applications via the chemical modification of synthetic pores with biological molecules. This article reviews some of the basis concepts and theories relevant to ion transport in nanopores with titratable charges stressing the analogies between synthetic pores and biological ion channels. The ultimate goal is to show that continuum theories may account for the essential features of these systems. A simple electrodiffusion model and its comparison with experimental results are chosen as a case study.

Ion size effects on the current efficiency of narrow charged pores

Abstract The effects of ion size on the current efficiency (CE) of charged membranes with narrow pores are studied theoretically. The CE is a measure of the membrane permselectivity defined as the ratio between the counterion flux and the sum of the counterion and coion fluxes when an electric potential difference is applied between the two solutions bathing the membrane. It is studied here as a function of two relevant experimental parameters: the ratio between the ionic radius and the pore radius, and the ratio between the external salt concentration and the membrane fixed charge concentration. The ratio of the CE values corresponding to the point and finite size ions is also calculated as a function of the above two parameters. Ion size effects are introduced in the ionic diffusion coefficients (by means of the Renkin function) as well as in the ionic concentration profiles. It is shown that a significantly higher coion exclusion from the membrane and thus a higher CE is obtained for finite size ions compared to the case of point ions.

Correct thermodynamic forces in Tsallis thermodynamics: connection with Hill nanothermodynamics

The equivalence between Tsallis thermodynamics and Hills nanothermodynamics is established. The correct thermodynamic forces in Tsallis thermodynamics are pointed out. Through this connection we also find a general expression for the entropic index q which we illustrate with two physical examples, allowing in both cases to relate q to the underlying dynamics of the Hamiltonian systems.

Charging a Capacitor from an External Fluctuating Potential using a Single Conical Nanopore

We explore the electrical rectification of large amplitude fluctuating signals by an asymmetric nanostructure operating in aqueous solution. We show experimentally and theoretically that a load capacitor can be charged to voltages close to 1 V within a few minutes by converting zero time-average potentials of amplitudes in the range 0.5-3 V into average net currents using a single conical nanopore. This process suggests that significant energy conversion and storage from an electrically fluctuating environment is feasible with a nanoscale pore immersed in a liquid electrolyte solution, a system characteristic of bioelectronics interfaces, electrochemical cells, and nanoporous membranes.

Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis.

Human carbamoyl phosphate synthetase (CPS1), a 1500-residue multidomain enzyme, catalyzes the first step of ammonia detoxification to urea requiring N-acetyl-L-glutamate (NAG) as essential activator to prevent ammonia/amino acids depletion. Here we present the crystal structures of CPS1 in the absence and in the presence of NAG, clarifying the on/off-switching of the urea cycle by NAG. By binding at the C-terminal domain of CPS1, NAG triggers long-range conformational changes affecting the two distant phosphorylation domains. These changes, concerted with the binding of nucleotides, result in a dramatic remodeling that stabilizes the catalytically competent conformation and the building of the ~35 Å-long tunnel that allows migration of the carbamate intermediate from its site of formation to the second phosphorylation site, where carbamoyl phosphate is produced. These structures allow rationalizing the effects of mutations found in patients with CPS1 deficiency (presenting hyperammonemia, mental retardation and even death), as exemplified here for some mutations.