Information Processing Schemes Based on Monolayer Protected Metallic Nanoclusters
Nanostructures are potentially useful as building blocks to complement future electronics because of their high versatility and packing densities. The fabrication and characterization of particular nanostructures and the use of new theoretical tools to describe their properties are receiving much attention. However, the integration of these individual systems into general schemes that could perform simple tasks is also necessary because modern electronics operation relies on the concerted action of many basic units. We review here new conceptual schemes that can allow information processing with ligand or monolayer protected metallic nanoclusters (MPCs) on the basis of the experimentally de…
Ionic circuitry with nanofluidic diodes
Ionic circuits composed of nanopores functionalized with polyelectrolyte chains can operate in aqueous solutions, thus allowing the control of electrical signals and information processing in physiological environments. We demonstrate experimentally and theoretically that different orientations of single-pore membranes with the same and opposite surface charges can operate reliably in series, parallel, and mixed series-parallel arrangements of two, three, and four nanofluidic diodes using schemes similar to those of solid-state electronics. We consider also different experimental procedures to externally tune the fixed charges of the molecular chains functionalized on the pore surface, show…
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…
Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics
AbstractBioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects …
The interplay between cooperativity and diversity in model threshold ensembles
The interplay between cooperativity and diversity is crucial for biological ensembles because single molecule experiments show a significant degree of heterogeneity and also for artificial nanostructures because of the high individual variability characteristic of nanoscale units. We study the cross-effects between cooperativity and diversity in model threshold ensembles composed of individually different units that show a cooperative behaviour. The units are modelled as statistical distributions of parameters (the individual threshold potentials here) characterized by central and width distribution values. The simulations show that the interplay between cooperativity and diversity results …
Associative Memory Based on Double-Gating of Molecularly Linked Nanosystem Arrays: A Theoretical Scheme
We discuss theoretically the properties of an associative memory (a system that can retrieve a stored pattern that is similar to the input pattern) based on the ideal conductive properties of a molecularly linked nanosystem array. Two schemes are considered for the memory based on the gate potential modulation of the drain-source current through the array. In the first scheme, the basic units of the electric circuit are nanosystems (e.g., nanoparticles) arranged in a series array. Each nanosystem is assumed to have two states of conductances, GM and Gm (GM ≫ Gm), that can be tuned externally by the gate and backgate potentials. The bit sequence associated with a given pattern is stored as t…
Precise mapping of the Goodpasture epitope(s) using phage display, site-directed mutagenesis, and surface plasmon resonance.
Goodpasture disease is an autoimmune disorder mediated by circulating autoantibodies against the noncollagenous-1 (NC1) domain of the alpha 3 chain of type IV collagen (alpha 3(IV)NC1). The structure of Goodpasture epitope(s) has been previously mapped into two main binding regions (E-A and E-B) of the alpha 3(IV)NC1 domain using a residue mutation approach on the highly related alpha 1(IV)NC1 domain. Here we combined phage display and surface plasmon resonance technology to more precisely localize the pathogenic binding sites. Peptides mimicking the Goodpasture epitope(s) were used to identify residues involved in autoantibody binding and found involvement of eight residues previously unre…
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.
Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate
Simple Summary Electric potential patterns across tissues are instructive for development, regeneration, and tumorigenesis because they can influence transcription, migration, and differentiation through biochemical and biomechanical downstream processes. Determining the origins of the spatial domains of distinct potential, which in turn decide anatomical features such as limbs, eyes, brain, and heart, is critical to a mature understanding of how bioelectric signaling drives morphogenesis. We studied theoretically how connexin proteins with different voltage-gated gap junction conductances can maintain multicellular regions at distinct membrane potentials. We analyzed a minimal model that i…
Size‐Based Cationic Molecular Sieving through Solid‐State Nanochannels
Advanced materials interfaces 8(6), 2001766 (2021). doi:10.1002/admi.202001766
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 tr…
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 asym…
Voltage-controlled current loops with nanofluidic diodes electrically coupled to solid state capacitors
[EN] We describe experimentally and theoretically voltage-controlled current loops obtained with nanofluidic diodes immersed in aqueous salt solutions. The coupling of these soft matter diodes with conventional electronic elements such as capacitors permits simple equivalent circuits which show electrical properties reminiscent of a resistor with memory. Different conductance levels can be reproducibly achieved under a wide range of experimental conditions (input voltage amplitudes and frequencies, load capacitances, electrolyte concentrations, and single pore and multipore membranes) by electrically coupling two types of passive components: the nanopores (ionics) and the capacitors (electr…
Ionic conduction through single-pore and multipore polymer membranes in aprotic organic electrolytes
Abstract We experimentally characterize the ionic conduction of single and multipore nanoporous membranes in aprotic organic electrolytes. To this end, soft-etched (SE) membranes with pore diameters in the nanometer range and track-etched (TE) membranes with pore diameters in the tens of nanometers range are investigated. In aqueous conditions, the membrane ionic conduction rates follow the same trend of the bulk solution conductivities. However, the ionic transport through the narrow SE-nanopores dramatically decreases in aprotic electrolytes due to the formation of solvated metal cations and their adsorption on the pore surface. The current-voltage recordings of single conical nanopores i…
Pore entrance effects on the electrical potential distribution in charged porous membranes and ion channels
Abstract Models for the electrical potential distribution in the interfacial region between a fixed charge membrane and an electrolyte solution have traditionally employed the Donnan equilibrium formalism that assumes discontinuous changes in concentrations and electric potential. In the case of the charged capillary membrane model, we propose to check rigorously the validity of this approach by solving the linearized Poisson–Boltzmann equation for the diffuse electrical double layer at the membrane|solution interface. The comparison of the resulting axial distribution for the electric potential with the Donnan potential drop shows that the discontinuous approach is only valid for membrane …
Concatenated logic functions using nanofluidic diodes with all-electrical inputs and outputs
[EN] Nanopore-based logical schemes in ionic solutions typically involve single gates and chemical inputs. The design of computer-like functions requires the consecutive concatenation of several gates and the use of electrical potentials and currents to facilitate the downstream transfer of electrochemical information. We have demonstrated the robust operation of concatenated logic functions using biomimetic nanofluidic diodes based on single pore membranes. To this end, we have implemented first the logic functions AND and OR with combinations of single nanopores using all-electrical input and output signals. The concatenation of these gates allows the output of the OR gate to act as one o…
Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly
15 páginas, 6 figuras, 1 tabla.
Biologically inspired information processing and synchronization in ensembles of non-identical threshold-potential nanostructures.
Nanotechnology produces basic structures that show a significant variability in their individual physical properties. This experimental fact may constitute a serious limitation for most applications requiring nominally identical building blocks. On the other hand, biological diversity is found in most natural systems. We show that reliable information processing can be achieved with heterogeneous groups of non-identical nanostructures by using some conceptual schemes characteristic of biological networks (diversity, frequency-based signal processing, rate and rank order coding, and synchronization). To this end, we simulate the integrated response of an ensemble of single-electron transisto…
Phosphorylation of the Goodpasture antigen by type A protein kinases.
Collagen IV is the major component of basement membranes. The human alpha 3 chain of collagen IV contains an antigenic domain called the Goodpasture antigen that is the target for the circulating immunopathogenic antibodies present in patients with Goodpasture syndrome. Characteristically, the gene region encoding the Goodpasture antigen generates multiple alternative products that retain the antigen amino-terminal region with a five-residue motif (KRGDS). The serine therein appears to be the major in vitro cAMP-dependent protein kinase phosphorylation site in the isolated antigen and can be phosphorylated in vitro by two protein kinases of approximately 50 and 41 kDa associated with human …
Membrane potential bistability in nonexcitable cells as described by inward and outward voltage-gated ion channels.
The membrane potential of nonexcitable cells, defined as the electrical potential difference between the cell cytoplasm and the extracellular environment when the current is zero, is controlled by the individual electrical conductance of different ion channels. In particular, inward- and outward-rectifying voltage-gated channels are crucial for cell hyperpolarization/depolarization processes, being amenable to direct physical study. High (in absolute value) negative membrane potentials are characteristic of terminally differentiated cells, while low membrane potentials are found in relatively depolarized, more plastic cells (e.g., stem, embryonic, and cancer cells). We study theoretically t…
Surface charge regulation of functionalized conical nanopore conductance by divalent cations and anions
Abstract The surface charge regulation in nanoscale volumes is a subject of wide interest to biological and chemical soft matter systems. Also, electrolyte mixtures with monovalent and divalent ions are commonplace in practical applications with micro and nanoporous ion-exchange membranes. We have studied experimentally and theoretically the conductance of conical nanopores functionalized with negative and positive surface charges that are bathed by electrolyte mixtures of the monovalent ions K+ and Cl− and the divalent ions Mg2+, Ba2+, Ca2+, and SO42−. Small concentrations of these ions can modulate the nanopore selectivity and conductance because of their interaction with the charged grou…
Fluoride-induced modulation of ionic transport in asymmetric nanopores functionalized with “caged” fluorescein moieties
[EN] We demonstrate experimentally and theoretically a nanofluidic fluoride sensing device based on a single conical pore functionalized with "caged" fluorescein moieties. The nanopore functionalization is based on an amine-terminated fluorescein whose phenolic hydroxyl groups are protected with tert-butyldiphenylsilyl (TBDPS) moieties. The protected fluorescein (Fcn-TBDPS-NH2) molecules are then immobilized on the nanopore surface via carbodiimide coupling chemistry. Exposure to fluoride ions removes the uncharged TBDPS moieties due to the fluoride-promoted cleavage of the silicon-oxygen bond, leading to the generation of negatively charged groups on the fluorescein moieties immobilized on…
Morphology changes induced by intercellular gap junction blocking: A reaction-diffusion mechanism.
Complex anatomical form is regulated in part by endogenous physiological communication between cells; however, the dynamics by which gap junctional (GJ) states across tissues regulate morphology are still poorly understood. We employed a biophysical modeling approach combining different signaling molecules (morphogens) to qualitatively describe the anteroposterior and lateral morphology changes in model multicellular systems due to intercellular GJ blockade. The model is based on two assumptions for blocking-induced patterning: (i) the local concentrations of two small antagonistic morphogens diffusing through the GJs along the axial direction, together with that of an independent, uncouple…
Sub-threshold signal processing in arrays of non-identical nanostructures
Weak input signals are routinely processed by molecular-scaled biological networks composed of non-identical units that operate correctly in a noisy environment. In order to show that artificial nanostructures can mimic this behavior, we explore theoretically noise-assisted signal processing in arrays of metallic nanoparticles functionalized with organic ligands that act as tunneling junctions connecting the nanoparticle to the external electrodes. The electronic transfer through the nanostructure is based on the Coulomb blockade and tunneling effects. Because of the fabrication uncertainties, these nanostructures are expected to show a high variability in their physical characteristics and…
Bioelectrical coupling in multicellular domains regulated by gap junctions: A conceptual approach.
We review the basic concepts involved in bioelectrically-coupled multicellular domains, focusing on the role of membrane potentials (Vmem). In the first model, single-cell Vmem is modulated by two generic polarizing and depolarizing ion channels, while intercellular coupling is implemented via voltage-gated gap junctions. Biochemical and bioelectrical signals are integrated via a feedback loop between Vmem and the transcription and translation of a protein forming an ion channel. The effective rate constants depend on the single-cell Vmem because these potentials modulate the local concentrations of signaling molecules and ions. This electrochemically-based idealization of the complex bioph…
Cesium-Induced Ionic Conduction through a Single Nanofluidic Pore Modified with Calixcrown Moieties
[EN] We demonstrate experimentally and theoretically a nanofluidic device for the selective recognition of the cesium ion by exploiting host¿guest interactions inside confined geometry. For this purpose, a host molecule, i.e., the amine-terminated p-tert-butylcalix[4]arene-crown (tBuC[4]C¿NH2), is successfully synthesized and functionalized on the surface of a single conical nanopore fabricated in a poly(ethylene terephthalate) (PET) membrane through carbodiimide coupling chemistry. On exposure to the cesium cation, the t-BuC[4]C¿Cs+ complex is formed through host¿guest interaction, leading to the generation of positive fixed charges on the pore surface. The asymmetrical distribution of the…
Innocampus Explora: Nuevas formas de comunicar ciencia
[EN] Innocampus Explora aims to show the students of the Burjassot-Paterna campus of the Universitat de València how the different scientific degrees are interrelated. To do this we propose activities in which students and teachers work together to cover the interdisciplinary nature of science, both in everyday and professional issues. Throughout this course the activities developed relate to new ways to communicate science. With the development of this project we contribute to a transversal quality education for all the participating students.
Nonlinear conductance and heterogeneity of voltage-gated ion channels allow defining electrical surface domains in cell membranes
Abstract The membrane potential of a cell measured by typical electrophysiological methods is only an average magnitude and experimental techniques allowing a more detailed mapping of the cell surface have shown the existence of spatial domains with locally different electric potentials and currents. Electrical potentials in non-neural cells are regulated by the nonlinear conductance of membrane ion channels. Voltage-gated potassium channels participate in cell hyperpolarization/depolarization processes and control the electrical signals over the cell surface, constituting good candidates to study basic biological questions on a more simplified scale than the complex cell membrane. These ch…
Individual Variability and Average Reliability in Parallel Networks of Heterogeneous Biological and Artificial Nanostructures
We simulate the collective electrical response of heterogeneous ensembles of biological and artificial nanostructures whose individual threshold potentials show a significant variability. This problem is of current interest because nanotechnology is bound to produce nanostructures with a significant experimental variability in their individual physical properties. This diversity is also present in biological systems that are however able to process information efficiently. The nanostructures considered are the ion channels of biological membranes, nanowire field-effect transistors, and metallic nanoparticle-based single electron transistors. These systems are simulated with canonical models…
Energy transduction and signal averaging of fluctuating electric fields by a single protein ion channel
[EN] We demonstrate the electrical rectification and signal averaging of fluctuating signals using a biological nanostructure in aqueous solution: a single protein ion channel inserted in the lipid bilayer characteristic of cell membranes. The conversion of oscillating, zero time-average potentials into directional currents permits charging of a load capacitor to significant steady-state voltages within a few minutes in the case of the outer membrane porin F (OmpF) protein, a bacterial channel of Escherichia coli. The experiments and simulations show signal averaging effects at a more fundamental level than the traditional cell and tissue scales, which are characterized by ensembles of many…
Reliable signal processing using parallel arrays of non-identical nanostructures and stochastic resonance
In the stochastic resonance (SR) phenomena, the response of a non-linear system to a weak periodic input signal is optimised by the presence of a particular level of noise which enhances signal detection. We explore, theoretically, the influence of thermal noise in arrays of metal nanoparticles functionalised with organic ligands acting as tunnelling junctions, with emphasis on the interplay between the SR phenomena and the nanostructure variability. In this system, the transference of a reduced number of electrons may suffice to implement a variety of electronic functions. However, because nanostructures are expected to show a significant variability in their physical characteristics, it i…
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 a…
Device variability and circuit redundancy in signal processing based on nanoswitches
Signal processing based on molecular switches whose conductance can be tuned by an external stimulus between two (on and off) states has been proposed recently (Cervera et al 2008 J. Appl. Phys. 104 084317). The basic building block is a metal nanoparticle linked to two electrodes by an organic ligand and a nanoswitch. The net charge delivered by this nanostructure exhibits a sharp resonance when the alternating potential applied between the electrodes has the same frequency as the periodic variation between the on and off conductance states induced on the nanoswitch. This resonance can be used to process an external signal by selectively extracting the weight of the different harmonics. Ho…
Impact of Surface Charge Directionality on Membrane Potential in Multi-ionic Systems
The membrane potential (Vmem), defined as the electric potential difference across a membrane flanked by two different salt solutions, is central to electrochemical energy harvesting and conversion. Also, Vmem and the ionic concentrations that establish it are important to biophysical chemistry because they regulate crucial cell processes. We study experimentally and theoretically the salt dependence of Vmem in single conical nanopores for the case of multi-ionic systems of different ionic charge numbers. The major advances of this work are (i) to measure Vmem using a series of ions (Na+, K+, Ca2+, Cl-, and SO42-) that are of interest to both energy conversion and cell biochemistry, (ii) to…
Carbohydrate-Mediated Biomolecular Recognition and Gating of Synthetic Ion Channels
Nanochannel-based biosensing devices have been proposed for selective detection of protein analyte molecules. However, the design and miniaturization of reusable channel-based biosensors is still a challenge in nanoscience and biotechnology. We present here a reusable nanofluidic biosensor based on reversible lectin-carbohydrate interactions. The nanochannels are fabricated in heavy ion tracked polymer membranes. The channel walls are functionalized with p-aminophenyl alpha-D-mannopyranoside (APMP) monolayers through carbodiimide coupling chemistry. The chemical (mannopyranoside) groups on the inner channel walls serve as binding sites and interact with specific protein molecules. The bindi…
Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model
Bioelectricity is emerging as a crucial mechanism for signal transmission and processing from the single-cell level to multicellular domains. We explore theoretically the oscillatory dynamics that result from the coupling between the genetic and bioelectric descriptions of nonexcitable cells in multicellular ensembles, connecting the genetic prepatterns defined over the ensemble with the resulting spatio-temporal map of cell potentials. These prepatterns assume the existence of a small patch in the ensemble with locally low values of the genetic rate constants that produce a specific ion channel protein whose conductance promotes the cell-polarized state (inward-rectifying channel). In this…
InnoCOVID-19: Primer congreso multidisciplinar Innocampus
[EN] The main objective of the educational innovation project Innocampus Explora is to show the existing interrelationship between the different scientific and technical degrees of Burjassot-Paterna campus of the University of Valencia. In this paper we present the InnoCOVID-19 Congress, activity organized during the 2020-21 academic year by the work team, made up of students and professors from all the Campus faculties.The objective of this conference, developed in virtual format, was to present the multidisciplinary projects that were formed on campus in response to the health crisis caused by the coronavirus SARS-CoV-2. This activity contributes to a quality transversal training for all …
Optimizing Energy Transduction of Fluctuating Signals with Nanofluidic Diodes and Load Capacitors
[EN] The design and experimental implementation of hybrid circuits is considered allowing charge transfer and energy conversion between nanofluidic diodes in aqueous ionic solutions and conventional electronic elements such as capacitors. The fundamental concepts involved are reviewed for the case of fluctuating zero-average external potentials acting on single pore and multipore membranes. This problem is relevant to electrochemical energy conversion and storage, the stimulus-response characteristics of nanosensors and actuators, and the estimation of the accumulative effects caused by external signals on biological ion channels. Half-wave and full-wave voltage doublers and quadruplers can…
The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles
AbstractThe single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and ele…
Bioelectrical model of head-tail patterning based on cell ion channels and intercellular gap junctions
Robust control of anterior-posterior axial patterning during regeneration is mediated by bioelectric signaling. However, a number of systems-level properties of bioelectrochemical circuits, including stochastic outcomes such as seen in permanently de-stabilized "cryptic" flatworms, are not completely understood. We present a bioelectrical model for head-tail patterning that combines single-cell characteristics such as membrane ion channels with multicellular community effects via voltage-gated gap junctions. It complements the biochemically-focused models by describing the effects of intercellular electrochemical coupling, cutting plane, and gap junction blocking of the multicellular ensemb…
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 reconfigurab…
Noise assisted image processing by ensembles of R-SETs
AbstractWe study how noise can assist the processing of an image in a resistance-single electron transistor (R-SET) model. The image is an 8-bit black and white picture. Every grey level is codified linearly into a sub-threshold input potential applied for a prescribed time window to an ensemble of R-SETs that transforms it into a spiking frequency. The addition of a background white noise potential of high amplitude permits the ensemble to process the image by means of the stochastic resonance phenomenon. Aside from the positive aspects, we analyse the negative impact of using noise and how we can minimize it using redundancy and a longer measuring time. The results are compared with the c…
Ionic transport characteristics of negatively and positively charged conical nanopores in 1:1, 2:1, 3:1, 2:2, 1:2, and 1:3 electrolytes
We study experimentally the current (I)-voltage (V) curves of 1:1, 2:1, 3:1, 2:2, 1:2, and 1:3 electrolytes in positively and negatively charged conically-shaped pores of nanoscale dimensions. The positive charges are poly(allylamine hydrochloride) chains functionalized on the pore surface by electrostatic interactions while the negative charges are carboxylic acid groups. Under physiological conditions, these fixed-charge groups are ionized and strongly interact with the different monovalent, divalent, and trivalent ions in the pore solution. The current rectification of the I-V curves and the membrane potentials provide fundamental information on the interaction of the pore charge groups …
Electrical Coupling in Ensembles of Nonexcitable Cells: Modeling the Spatial Map of Single Cell Potentials
We analyze the coupling of model nonexcitable (non-neural) cells assuming that the cell membrane potential is the basic individual property. We obtain this potential on the basis of the inward and outward rectifying voltage-gated channels characteristic of cell membranes. We concentrate on the electrical coupling of a cell ensemble rather than on the biochemical and mechanical characteristics of the individual cells, obtain the map of single cell potentials using simple assumptions, and suggest procedures to collectively modify this spatial map. The response of the cell ensemble to an external perturbation and the consequences of cell isolation, heterogeneity, and ensemble size are also ana…
PINK1 displays tissue-specific subcellular location and regulates apoptosis and cell growth in breast cancer cells.
The PINK1 gene is mutated in the germ line of patients with hereditary early-onset Parkinson disease, and PINK1 prosurvival function at neuronal mitochondria has been related with the etiology of this disease. However, the expression and function of PINK1 protein in nonneuronal tissues has not been determined yet. Here, we have analyzed PINK1 protein expression and subcellular distribution in normal and neoplastic human tissues and investigated the function of PINK1 in breast carcinoma cells. PINK1 protein, as stained by a specific anti-PINK1 monoclonal antibody, was widely expressed in human tissues, displaying high expression in epithelial tissues and in the central nervous system and low…
Tetraalkylammonium Cations Conduction through a Single Nanofluidic Diode: Experimental and Theoretical Studies
[EN] We describe experimentally and theoretically the concentration-dependent conduction of tetraalkylammonium (TAA+) cations through a nanofluidic diode fabricated in a polymer membrane via asymmetric track-etching techniques. This single-pore membrane exhibits current rectification characteristics because of the ionized carboxylate groups on the pore surface. We use aqueous solutions of potassium (K+ ), ammonium (A+ ), tetramethylammonium (TMA+ ), tetraethylammonium (TEA+ ), and tetrabutylammonium (TBA+ ) ions with concentrations ranging from 50 to 500 mM under acidic (pH 3.5) and physiological (pH 6.5) conditions. Compared with the K+ and A+ ions, the TMA+ , TEA+ , and TBA+ ions show rel…
Nanopore charge inversion and current-voltage curves in mixtures of asymmetric electrolytes
[EN] We consider the screening of the negative charges (carboxylic acid groups) fixed on the surface of a conical-shaped track-etched nanopore by divalent magnesium (Mg2+) and trivalent lanthanum (La3+). The experimental current (I)-voltage (V) curves and current rectification ratios allow discussing fundamental questions about the overcompensation of spatially-fixed charges by multivalent ions over nanoscale volumes. The effects of charge inversion or reversal on nanopore transport are discussed in mixtures of asymmetric electrolytes (LaCl3 and MgCl2 with KCl). In particular, pore charge inversion is demonstrated for La3+ as well as for mixtures of this trivalent ion at low concentrations …
Metallic Nanoparticles Linked to Molecular Switches as Signal Processing Devices
We explore theoretically the use of nanoscale switches whose conductance can be varied between two states by an external stimulus to implement signal processing devices. The building block is formed by a metallic nanoparticle linked to two electrodes by an organic ligand and a molecular switch. The system implementation exploits the sharp current resonance of the system that occurs when the frequencies of the applied potential and the induced variation on the switch conductance coincide.
Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs
The targeting of the tumor suppressor PTEN protein to distinct subcellular compartments is a major regulatory mechanism of PTEN function, by controlling its access to substrates and effector proteins. Here, we investigated the molecular basis and functional consequences of PTEN nuclear/cytoplasmic distribution. PTEN accumulated in the nucleus of cells treated with apoptotic stimuli. Nuclear accumulation of PTEN was enhanced by mutations targeting motifs in distinct PTEN domains, and it was dependent on an N-terminal nuclear localization domain. Coexpression of a dominant negative Ran GTPase protein blocked PTEN accumulation in the nucleus, which was also affected by coexpression of importin…
Cooperative Effects Enhance Electric-Field-Induced Conductance Switching in Molecular Monolayers
The anchoring of molecules with functional groups at surfaces permits information processing based on two stable molecular states that can be tuned externally by light irradiation and external fields. By using a molecular model that incorporates the essential characteristics of the problem, we show that the local interactions between adjacent molecules in a densely packed monolayer can stabilize domains with the same molecular state because of cooperative processes, enhancing significantly the switching properties between the molecular states. The case of electric-field-induced conductance switching is exploited in two possible applications: the design of a logic gates system and the operat…
Converting external potential fluctuations into nonzero time-average electric currents using a single nanopore
The possibility of taking advantage of a fluctuating environment for energy and information transduction is a significant challenge in biological and artificial nanostructures. We demonstrate here directional electrical transduction from fluctuating external signals using a single nanopore of conical shape immersed in an ionic aqueous solution. To this end, we characterize experimentally the average output currents obtained by the electrical rectification of zero time-average input potentials. The transformation of external potential fluctuations into nonzero time-average responses using a single nanopore in liquid state is of fundamental significance for biology and nanophysics. This energ…
Innocampus Explora: Una aproximación multidisciplinar a la problemática ambiental
[ES] Presentamos las actividades del proyecto de innovación Innocampus Explora desarrollado en el campus de Burjassot-Paterna de la Universitat de València y cuyo objetivo principal es mostrar la interrelación existente entre los diferentes grados científicos y técnicos del campus. En la presente anualidad, el equipo de trabajo integrado por estudiantes y profesores de todos las facultades y escuelas del campus de Burjassot-Paterna, ha desarrollado actividades en torno a la problemática medioambiental. Una visión transversal e interdisciplinar de los problemas de los usos del plástico y de la energía nuclear que enlaza con varios de los Objetivos de Desarrollo Sostenible (ODS) dictados por …
Distribution potential in electrified microemulsions with potential determining salts
Abstract The electrical polarization of lamellar and water-in-oil microemulsions composed of the aqueous solution of a potential determining salt (PDS), an organic solvent and a nonionic surfactant has been studied. The distribution of the PDS ions across the interface between two immiscible electrolyte solutions (ITIES) generates an electrical potential difference which can be used to control charge transfer processes. In macroscopic ITIES, this distribution potential is independent of the PDS concentration and can be determined from the electroneutrality condition far from the interface. In microemulsions, on the contrary, the distribution potential is smaller in magnitude and depends on …
Polarity and bioelectrical patterning in a linear chain of non-excitable cells
Abstract Polarity in multicellular systems is influenced by bioelectrical signals because electric potentials can act as spatio-temporal patterns for other biochemical processes that eventually emerge as long-lasting biological outcomes. We study the role of the electric potential in establishing head-tail polarity for the case of a chain of non-excitable cells. This biophysical model incorporates both single-cell (membrane ion channels) and multicellular (intercellular gap junctions) characteristics. The results are presented in the form of a bioelectrical phase space that complements traditional biochemical approaches and provides qualitative insights for the case of anterior/posterior po…
Emprendimiento Social en Ciencias de la Salud: Creación del Aula ApS-Salud en la Facultad de Farmacia de la Universitat de València.
[EN] Service-Learning (SL) aligned to Sustainable Development Goals (SDG) is an educational tool that is used in the Faculty of Pharmacy of the University of Valencia in an interdisciplinary way. The Study Plans of the five Degrees taught in this center do not explicitly cover subjects or content in entrepreneurship, business creation and / or development of projects that may originate business.However, there are certain contents that are oriented in a different way could be used to promote these abilities in students. SL-Health Classroom aims to cover this aspect and has been created with the aim of designing, planning and executing SL projects that serve as a driving idea for a subsequent…
Electrical network of nanofluidic diodes in electrolyte solutions: Connectivity and coupling to electronic elements
[EN] We consider a nanopore network with simple connectivity, demonstrating a two-dimensional circuit (full-wave rectifier) with ensembles of conical pores acting as nanofluidic diodes. When the bridge nanopore network is fed with an input potential signal of fluctuating polarity, a fixed output polarity is obtained. The full-wave rectification characteristics are demonstrated with square, sinusoidal, and white noise input waveforms. The charging of a load capacitor located between the two legs of the bridge demonstrates that the nanofluidic network is effectively coupled to this electronic element. These results can be relevant for energy transduction and storage procedures with nanopores …
Blocking of an ion channel by a highly charged drug: Modeling the effects of applied voltage, electrolyte concentration, and drug concentration
We present a simple physical model to estimate the blocked pore probability of an ion channel that can be blocked by a highly charged drug in solution. The model is inspired by recent experimental work on the blocking of the ${\mathrm{PA}}_{63}$ channel, involved in the anthrax toxin infection, by a highly charged drug [Karginov et al. PNAS 102, 15075 (2005)]. The drug binding to the pore is highly specific but the strong dependence of blocking on the applied voltage and electrolyte concentration suggests that long range electrostatic interactions are important. Since basic electrostatic concepts rather than detailed molecular models are considered, the microscopic details of the channel bl…
Bioelectrical Coupling of Single-Cell States in Multicellular Systems.
The spatiotemporal distributions of signaling ions and molecules that modulate biochemical pathways in nonexcitable cells are influenced by multicellular electric potentials. These potentials act as distributed controllers encoding instructive spatial patterns in development and regeneration. We review experimental facts and discuss recent bioelectrical models that provide new physical insights and complement biochemical approaches. Single-cell states are modulated at the multicellular level because of the coupling between neighboring cells, thus allowing memories and multicellular patterns. The model is based on (i) two generic voltage-gated ion channels that promote the polarized and depo…
Calculation of the wetting parameter from a cluster model in the framework of nanothermodynamics
The critical wetting parameter ${\ensuremath{\omega}}_{c}$ determines the strength of interfacial fluctuations in critical wetting transitions. In this Brief Report, we calculate ${\ensuremath{\omega}}_{c}$ from considerations on critical liquid clusters inside a vapor phase. The starting point is a cluster model developed by Hill and Chamberlin in the framework of nanothermodynamics [Proc. Natl. Acad. Sci. USA 95, 12779 (1998)]. Our calculations yield results for ${\ensuremath{\omega}}_{c}$ between 0.52 and 1.00, depending on the degrees of freedom considered. The findings are in agreement with previous experimental results and give an idea of the universal dynamical behavior of the cluste…
Asymmetric nanopore rectification for ion pumping, electrical power generation, and information processing applications
Single-track, asymmetric nanopores can currently be functionalised with a spatially inhomogeneous distribution of fixed charges and a variety of pore tip shapes. Optimising the asymmetric nanopore characteristics is crucial for practical applications in nanofluidics. We have addressed here this question for three cases based on different input/output chemical and electrical signals: (i) ion pumping up a concentration gradient by means of a periodic, time-dependent bias potential, (ii) information processing with a single nanopore acting as the nanofluidic diode of a logic gate, and (iii) electrical energy harvesting using a nanopore that separates two solutions of different salt concentrati…
Effect of cationic polyamidoamine dendrimers on ionic transport through nanochannels
Abstract The effect of polyamidoamine (PAMAM) dendrimers (generations G0–G3) on the ion transport properties of nanochannels (conical and cylindrical) is studied either by surface functionalization or by addition to the electrolyte solution. Surface functionalization with cationic dendrimers lead to inversion of the ion current rectification, indicating the anion selectivity of the modified nanochannels. This anion selectivity increases by immobilizing higher-generation dendrimers, as expected for an increase in the surface density of amino groups. However, compared to PAMAM G2, functionalization with PAMAM G3 results in higher cation and lower anion fluxes. Diffusion experiments of charged…
Logic Functions with Stimuli-Responsive Single Nanopores
[EN] We present the concept of logic functions based on a single stimuli-responsive nanopore and analyze its potential for electrochemical transducers and actuators. The responsive molecules at the surface of the polymeric nanopore immersed in an electrolyte solution are sensitive to thermal, chemical, electrical, and optical stimuli, which are the input signals required to externally tune the conductance of the nanopore (the logical output). A single nanostructure can be operated as a resistor or as a diode with a broad range of rectifying properties, allowing for logical information-processing schemes that are useful pH and temperature sensors, electro-optical detectors, and electrochemic…
Characterization and Expression of Multiple Alternatively Spliced Transcripts of the Goodpasture Antigen Gene Region. Goodpasture Antibodies Recognize Recombinant Proteins Representing the Autoantigen and One of its Alternative Forms
Collagen IV, the major component of basement membranes, is composed of six distinct alpha chains (alpha 1-alpha 6). Atypically among the collagen IV genes, the exons encoding the carboxyl-terminal region of the human alpha 3(IV) chain undergo alternative splicing. This region has been designated as the Goodpasture antigen because of its reactivity in the kidney and lung with the pathogenic autoantibodies causing Goodpasture syndrome. The data presented in this report demonstrate that, in human kidney, the gene region encompassing the Goodpasture antigen generates at least six alternatively spliced transcripts predicting five distinct proteins that differ in their carboxyl-terminus and retai…
Energy conversion from external fluctuating signals based on asymmetric nanopores
Electrical transduction from fluctuating external signals is central to energy conversion based on nanoscale electrochemical devices and bioelectronics interfaces. We demonstrate theoretically and experimentally a significant energy transduction from white noise signals using the electrical rectification of asymmetric nanopores in polymeric membranes immersed in aqueous electrolyte solutions. Load capacitor voltages of the order of 1 V are obtained within times of the order of 1 min by means of nanofluidic diodes which convert zero time-average potentials of amplitudes of the order of 1 V into average net currents. We consider single-nanopore and multipore membranes to show that the convers…
Community effects allow bioelectrical reprogramming of cell membrane potentials in multicellular aggregates: Model simulations.
Bioelectrical patterns are established by spatiotemporal correlations of cell membrane potentials at the multicellular level, being crucial to development, regeneration, and tumorigenesis. We have conducted multicellular simulations on bioelectrical community effects and intercellular coupling in multicellular aggregates. The simulations aim at establishing under which conditions a local heterogeneity consisting of a small patch of cells can be stabilized against a large aggregate of surrounding identical cells which are in a different bioelectrical state. In this way, instructive bioelectrical information can be persistently encoded in spatiotemporal patterns of separated domains with diff…
Fabrication of soft-etched nanoporous polyimide membranes for ionic conduction and discrimination
Abstract Ionic selectivity in nanopores is usually based either on steric or charge exclusion mechanisms. By simultaneously incorporating both mechanisms into a functionalized membrane, an improved control over selectivity can be achieved. We describe the fabrication and experimental characterization of alkali metal cation-selective nanopores in heavy ion-tracked polyimide (PI) membranes using the soft-etching (SE) technique. The latent ion tracks in the PI membrane are selectively dissolved by an organic solvent to form tiny pores without affecting the bulk material. The ionic transport properties of SE-PI membranes are characterized using different electrolyte solutions containing alkali …
Multipore membranes with nanofluidic diodes allowing multifunctional rectification and logical responses
[EN] We have arranged two multipore membranes with conical nanopores in a three-compartment electrochemical cell. The membranes act as tunable nanofluidic diodes whose functionality is entirely based on the pH-reversed ion current rectification and does not require specific surface functionalizations. This electrochemical arrangement can display different electrical behaviors (quasi-linear ohmic response and inward/outward rectifications) as a function of the electrolyte concentration in the external solutions and the applied voltage at the pore tips. The multifunctional response permits to implement different logical responses including NOR and INHIBIT functions.
Multivalued and Reversible Logic Gates Implemented with Metallic Nanoparticles and Organic Ligands
Modeling Information Processing Using Nonidentical Coulomb Blockade Nanostructures
In recent years, molecular-protected metallic nanoparticles (NPs) have attracted a great deal of attention. Because of their reduced size, they behave like tiny capacitors so that there is an energy penalty when adding an electron to the NP which suppresses the electric current at a potential lower than a threshold value. This phenomenon is known as Coulomb blockade (CB) and allows the transport of electrons to be modulated through an external gate provided that the energy penalty is higher than the thermal energy. Together with the possibility of tailoring their properties, molecular protected NPs are potential candidates as future components of high density, low consumption electronics. H…
Electrical fluctuations in monolayer-protected metal nanoclusters
Abstract Monolayer-protected clusters (MPCs) are formed by a neutral or charged metallic core surrounded by an organic ligand monolayer. We estimate the electric potential fluctuations of a MPC in an electrolyte solution by using the equilibrium fluctuation–dissipation theorem and the non-linear Poisson–Boltzmann equation extended to account for ion penetration in the monolayer. Significant fluctuations are predicted because the MPC capacitance is small (approximately 1 aF). We study also the non-equilibrium case of a MPC sandwiched between two electrodes and estimate the current noise considering the nanocluster as a single electron transistor and using a theoretical approach based on the …
Ion size effects on the electrokinetic flow in nanoporous membranes caused by concentration gradients
The space charge model (SCM) relies on the Poisson−Boltzmann (PB) equation, and hence on the assumption of negligible ion size effects, to calculate the radial distribution of the electrical potent...
Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly. Corrigendum
The article by Casino et al. [IUCrJ (2018). 5, 765–779] is corrected.
Signal processing and frequency-dependent associative memory based on nanoswitches
A signal processing concept based on nanoscale switches whose conductance can be tuned by an external stimulus between two (ON and OFF) states is proposed and analyzed theoretically. The building block of the system is formed by a metal nanoparticle linked to two electrodes by an organic ligand and a molecular switch. When we apply an alternating potential to the system of the same frequency as the periodic variation between the ON and OFF states induced on the switch, the net charge delivered by the system exhibits a sharp resonance. This resonance can be used to process an external signal by selectively extracting the weight of the different harmonics. In addition, a frequency-dependent a…
Negative differential resistance and threshold-switching in conical nanopores with KF solutions
Negative differential resistance (NDR) phenomena are under-explored in nanostructures operating in the liquid state. We characterize experimentally the NDR and threshold switching phenomena observed when conical nanopores are immersed in two identical KF solutions at low concentration. Sharp current drops in the nA range are obtained for applied voltages exceeding thresholds close to 1 V and a wide frequency window, which suggests that the threshold switching can be used to amplify small electrical perturbations because a small change in voltage typically results in a large change in current. While we have not given a detailed physical mechanism here, a phenomenological model is also includ…
The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching On/Off the Urea Cycle
12 páginas, 4 figuras, 2 tablas.
Scanning electrochemical microscopy as a probe of Ag+ binding kinetics at Langmuir phospholipid monolayers
A new method has been developed for measuring local adsorption rates of metal ions at interfaces based on scanning electrochemical microscopy (SECM). The technique is illustrated with the example of Ag+ binding at Langmuir phospholipid monolayers formed at the water/air interface. Specifically, an inverted 25 microm diameter silver disc ultramicroelectrode (UME) was positioned in the subphase of a Langmuir trough, close to a dipalmitoyl phosphatidic acid (DPPA) monolayer, and used to generate Ag+ via Ag electro-oxidation. The method involved measuring the transient current-time response at the UME when the electrode was switched to a potential to electrogenerate Ag+. Since the Ag+/Ag couple…
Modulation of current-time traces by two-pore arrangements of polyimide nanofluidic diodes
Liquid state arrangements of two polymeric membranes with single conical nanopores constitute nanofluidic diodes that allow a rich electrical functionality based on the modulation of individual conductances in aqueous electrolyte solutions. In particular, the prescribed sequences of current-time traces can be obtained by preprogramed switching between series and parallel pore connection arrangements. Hybrid nanopore-solid-state circuits are also possible. The basic applied physics of the nanofluidic diode arrangements can be understood from simple circuit theory concepts and should be of widespread interest to sensing and actuating procedures, controlled release dispensers, and energy conve…
Logic gates scheme based on Coulomb blockade in metallic nanoclusters with organic ligands
We propose a logic gates scheme based on the electron transfer through metallic nanoclusters linked to organic ligands and discuss theoretically the characteristics needed for practical implementation. As a proof-of-the-concept, we demonstrate the OR, AND and NOT gates and study the performance in terms of temperature, applied voltage, and noise.
Correct thermodynamic forces in Tsallis Thermodynamics: connection with Hill Nanothermodynamics
The equivalence between Tsallis Thermodynamics and Hill 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.
Fluoride-Induced Negative Differential Resistance in Nanopores: Experimental and Theoretical Characterization
We describe experimentally and theoretically the fluoride-induced negative differential resistance (NDR) phenomena observed in conical nanopores operating in aqueous electrolyte solutions. The threshold voltage switching occurs around 1 V and leads to sharp current drops in the nA range with a peak-to-valley ratio close to 10. The experimental characterization of the NDR effect with single pore and multipore samples concern different pore radii, charge concentrations, scan rates, salt concentrations, solvents, and cations. The experimental fact that the effective radius of the pore tip zone is of the same order of magnitude as the Debye length for the low salt concentrations used here is su…
HCN2 Channel-Induced Rescue of Brain Teratogenesis via Local and Long-Range Bioelectric Repair
Embryonic exposure to the teratogen nicotine results in brain defects, by disrupting endogenous spatial pre patterns necessary for normal brain size and patterning. Extending prior work in Xenopus laevis that showed that misexpression of ion channels can rescue morphogenesis, we demonstrate and characterize a novel aspect of developmental bioelectricity: channel-dependent repair signals propagate long-range across the embryo. We show that distal HCN2 channel misexpression and distal transplants of HCN2-expressing tissue, non-cell-autonomously reverse profound defects, rescuing brain anatomy, gene expression, and learning. Moreover, such rescue can be induced by small-molecule HCN2 channel a…
Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicellular oscillations.
Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemb…
From non-excitable single-cell to multicellular bioelectrical states supported by ion channels and gap junction proteins: Electrical potentials as distributed controllers.
Endogenous bioelectric patterns within tissues are an important driver of morphogenesis and a tractable component of a number of disease states. Developing system-level understanding of the dynamics by which non-neural bioelectric circuits regulate complex downstream cascades is a key step towards both, an evolutionary understanding of ion channel genes, and novel strategies in regenerative medicine. An important capability gap is deriving rational modulation strategies targeting individual cells' bioelectric states to achieve global (tissue- or organ-level) outcomes. Here, we develop an ion channel-based model that describes multicellular states on the basis of spatio-temporal patterns of …
Kinetic modeling of ion conduction in KcsA potassium channel.
KcsA constitutes a potassium channel of known structure that shows both high conduction rates and selectivity among monovalent cations. A kinetic model for ion conduction through this channel that assumes rapid ion transport within the filter has recently been presented by Nelson. In a recent, brief communication, we used the model to provide preliminary explanations to the experimental current-voltage J-V and conductance-concentration g-S curves obtained for a series of monovalent ions (K(+),Tl(+), and Rb(+)). We did not assume rapid ion transport in the calculations, since ion transport within the selectivity filter could be rate limiting for ions other than native K(+). This previous wor…
A signal processing scheme based on high-frequency electromechanical oscillations in nanostructures
We explore the characteristics of a new signal processing scheme based on the high-frequency electromechanical oscillations of a nanostructure formed by an oscillating metallic nanoparticle connected to the left and right electrodes by soft links. Because this system shows resonant behavior when the frequency of the applied electric potential is close to the characteristic natural frequency of the oscillating nanoparticle, a parallel arrangement of nanostructures with different frequencies can be excited selectively by an external time-dependent electrical signal with the appropriate resonant frequencies. The highly nonlinear system response makes it possible to devise a signal processing s…
Membrane potential of single asymmetric nanopores: Divalent cations and salt mixtures
We study the electric potential difference (membrane potential) that arises across a single-pore membrane which separates two aqueous solutions at different salt concentrations. This potential difference is obtained here as the reversal potential of a conical nanopore, defined as the applied voltage needed to obtain a zero current through the membrane. To this end, different monovalent (LiCl, NaCl, KCl, and CsCl) and divalent (CaCl2, MgCl2, and BaCl2) cations are considered over a wide range of concentrations and salt mixtures for the two asymmetric nanostructure directionalities. The experimental data allows discussing fundamental questions on the interaction of the charges fixed to the po…
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 descriptio…
Synchronization of Bioelectric Oscillations in Networks of Nonexcitable Cells: From Single-Cell to Multicellular States.
Biological networks use collective oscillations for information processing tasks. In particular, oscillatory membrane potentials have been observed in nonexcitable cells and bacterial communities where specific ion channel proteins contribute to the bioelectric coordination of large populations. We aim at describing theoretically the oscillatory spatiotemporal patterns that emerge at the multicellular level from the single-cell bioelectric dynamics. To this end, we focus on two key questions: (i) What single-cell properties are relevant to multicellular behavior? (ii) What properties defined at the multicellular level can allow an external control of the bioelectric dynamics? In particular,…
Heterogeneous lack of expression of the tumour suppressor PTEN protein in human neoplastic tissues.
PTEN, a tumour suppressor gene located at chromosome 10q23 and commonly mutated or deleted in a variety of tumours, encodes a dual-specific/phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase. We report the generation of an anti-PTEN monoclonal antibody (MAb) that recognises an epitope at the C-terminus of PTEN, and describe the heterogeneous lack of expression of the PTEN protein in human tumour tissues, as demonstrated by immunohistochemical methods. Our anti-PTEN MAb provides a useful tool for the study of PTEN protein expression in tumour samples, in the search for tumour prognostic molecular markers.
Synchronization of coupled single-electron circuits based on nanoparticles and tunneling junctions
We explore theoretically the synchronization properties of a device composed of coupled single-electron circuits whose building blocks are nanoparticles interconnected with tunneling junctions. Elementary nanoscillators can be achieved by a single-electron tunneling cell where the relaxation oscillation is induced by the tunneling. We develop a model to describe the synchronization of the nanoscillators and present sample calculations to demonstrate that the idea is feasible and could readily find applications. Instead of considering a particular system, we analyze the general properties of the device making use of an ideal model that emphasizes the essential characteristics of the concept.…
Coupling theory for counterion distributions based in Tsallis statistics
It is well known that the Poisson-Boltzmann (PB) equation yields the exact counterion density around charged objects in the weak coupling limit. In this paper we generalize the PB approach to account for coupling of arbitrary strength by making use of Tsallis q-exponential distributions. Both the weak coupling and the strong coupling limits are reproduced. For arbitrary coupling we also provide simple analytical expressions which are compared to recent Monte Carlo simulations by A. G. Moreira and R. R. Netz [Europhys. Lett. 52 (2000) 705]. Excellent agreement with these is obtained.
MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity.
We have studied theoretically the microRNA (miRNA) intercellular transfer through voltage-gated gap junctions in terms of a biophysically grounded system of coupled differential equations. Instead of modeling a specific system, we use a general approach describing the interplay between the genetic mechanisms and the single-cell electric potentials. The dynamics of the multicellular ensemble are simulated under different conditions including spatially inhomogeneous transcription rates and local intercellular transfer of miRNAs. These processes result in spatiotemporal changes of miRNA, mRNA, and ion channel protein concentrations that eventually modify the bioelectrical states of small multi…