0000000000164297
AUTHOR
Antonio Alcaraz
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 …
Electric field enhanced water dissociation at the bipolar membrane junction from ac impedance spectra measurements
Abstract Preliminary experimental results of the ac impedance spectra of a bipolar ion-exchange membrane are reported and interpreted on the basis of a previous theoretical model based on the Nernst–Planck/Poisson equations. It is shown that the experiments can provide valuable electrochemical information about the bipolar junction structure and the electric-field enhanced water dissociation phenomenon that occurs at this junction, although the high number of unknown parameters involved makes it difficult to obtain accurate values for the parameters characteristic of this phenomenon.
Electrical Pumping of Potassium Ions Against an External Concentration Gradient in a Biological Ion Channel
We show experimentally and theoretically that significant currents can be obtained with a biological ion channel, the OmpF porin of Escherichia coli, using zero-average potentials as driving forces. The channel rectifying properties can be used to pump potassium ions against an external concentration gradient under asymmetric pH conditions. The results are discussed in terms of the ionic selectivity and rectification ratio of the channel. The physical concepts involved may be applied to separation processes with synthetic nanopores and to bioelectrical phenomena. (C) 2013 AIP Publishing LLC.
Effects of pH on ion transport in weak amphoteric membranes
Abstract We have studied theoretically the effect of pH on the ion transport through amphoteric polymer membranes composed of weak polyelectrolytes where the charged groups are randomly distributed along the axial direction of the membrane. This system serves as a simplified model for the pH controlled ion transport and drug delivery through membranes of biological interest. The theoretical approach employed is based on the Nernst-Planck equations. The complete system of electrical charges formed by: (i) the pH dependent, amphoretic membrane fixed charge, and (ii) the four mobile charges (the salt ions and the hydrogen and hydroxide ions) have been taken into account without any additional …
Donnan equilibrium of ionic drugs in pH-dependent fixed charge membranes: theoretical modeling.
Abstract We have studied theoretically the partition equilibrium of a cationic drug between an electrolyte solution and a membrane with pH-dependent fixed charges using an extended Donnan formalism. The aqueous solution within the fixed charge membrane is assumed to be in equilibrium with an external aqueous solution containing six ionic species: the cationic drug (DH + ), the salt cations (Na + and Ca 2+ ), the salt anion (Cl − ), and the hydrogen and hydroxide ions. In addition to these mobile species, the membrane solution may also contain four fixed species attached to the membrane chains: strongly acid sulfonic groups (SO 3 − ), weakly acid carboxylic groups in dissociated (COO − ) a…
A pH-tunable nanofluidic diode: electrochemical rectification in a reconstituted single ion channel.
We report pH-dependent electrochemical rectification in a protein ion channel (the bacterial porin OmpF) reconstituted on a planar phospholipid membrane. The measurements performed at single-channel level show that the electric current is controlled by the protein fixed charge and it can be tuned by adjusting the local pH. Under highly asymmetric pH conditions, the channel behaves like a liquid diode. Unlike other nanofluidic devices that display also asymmetric conductance, here the microscopic charge distribution of the system can be explored by using the available high-resolution (2.4 A) channel crystallographic structure. Continuum electrostatics calculations confirm the hypothesized bi…
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…
Simple molecular model for the binding of antibiotic molecules to bacterial ion channels
A molecular model aimed at explaining recent experimental data by Nestorovich et al. [Proc. Natl. Acad. Sci. USA 99, 9789 (2002)] on the interaction of ampicillin molecules with the constriction zone in a channel of the general bacterial porin, OmpF (outer membrane protein F), is presented. The model extends T. L. Hill’s theory for intermolecular interactions in a pair of binding sites [J. Am. Chem. Soc. 78, 3330 (1956)] by incorporating two binding ions and two pairs of interacting sites. The results provide new physical insights on the role of the complementary pattern of the charge distributions in the ampicillin molecule and the narrowest part of the channel pore. Charge matching of int…
Conductive and Capacitive Properties of the Bipolar Membrane Junction Studied by AC Impedance Spectroscopy
The complete ac impedance spectrum of four bipolar membranes is analyzed both theoretically and experimentally taking into account both ionic transport and water dissociation together with the structural aspects of the bipolar junction. A theoretical model based on the Nernst-Planck and Poisson equations for the conductive and capacitive properties of the junction provides a qualitative description of the bipolar membranes for a broad range of electric currents and temperatures. Special attention is paid to the characteristics of the bipolar junction structure and the contact region between the two ion-exchange layers. It is observed that the effective area of this region increases with the…
pH and supporting electrolyte concentration effects on the passive transport of cationic and anionic drugs through fixed charge membranes
Abstract The effects of pH and supporting electrolyte concentration on the passive transport of an ionized (cationic or anionic) drug through a thick fixed charge membrane have been theoretically studied. This system constitutes a simplified model for the pH controlled ion transport and drug delivery through membranes of biological and pharmaceutical interest. Calculations were carried out for different values of the membrane fixed charge, supporting electrolyte and drug concentrations covering a broad range of the conditions usually found in experiments. The theoretical approach employed is based on the Nernst–Planck flux equations, and all of the species present in the system (the neutral…
Effects of water dielectric saturation on the space–charge junction of a fixed-charge bipolar membrane
Abstract The dielectric saturation at the space–charge junction of a fixed-charge bipolar membrane is studied using the theoretical approach by Booth for the water dielectric constant and the Poisson equation for the electrical double layer at the junction. The numerical solution gives the electric field and dielectric constant profiles through the junction as well as the junction thickness as a function of the voltage drop. The water dielectric constant decreases substantially for the large electric fields that may occur at the narrow bipolar junction.
Saving banks and society: a model of commitment to society
Savings banks are increasingly interested in social issues, reflecting a corporate commitment to meet the demands of society. Our goal is to understand the importance of CSR (Corporate Social Responsibility) for savings banks and the actions carried out to promote it. To do this we assume that these entities are more resources devoted to society. The field work was conducted through a questionnaire answered by 57 Spanish institutions. We note that CSR is a growing movement with enormous potential, because of the role of financial intermediation and lending banks to develop. Finally, it is curious to see how social contributions materialize so correlated. Las Cajas de Ahorros tienen cada vez…
Electric field-assisted proton transfer and water dissociation at the junction of a fixed-charge bipolar membrane
Abstract Electric field-enhanced (EFE) water dissociation can occur at the interfacial space charge junction of both biological and synthetic fixed-charge bipolar membranes. This dissociation has so far been analysed on an electrochemical basis using modified second Wien effect and absolute rate theories. We propose a statistical thermodynamics model to describe the cooperative orientation of the water molecules by the electric field at the bipolar junction. The approach is simple and retains some of the essential aspects of the phenomenon. In particular, the EFE water dissociation can now be rationalised on the basis of a field-assisted proton transfer mechanism involving the membrane fixe…
A Simple Model for Ac Impedance Spectra in Bipolar Membranes
A new model accounting for the ac impedance spectra of synthetic ion-exchange bipolar membranes is presented. The theoretical approach is based on the Nernst−Planck and Poisson equations and applies some of the concepts used in the semiconductor pn junctions to the case of a bipolar membrane. The results presented are the current−voltage curves and the impedance spectra at electric currents above the limiting current. It is shown that the model is able to identify the main contributions to the bipolar membrane impedance and gives valuable information about the bipolar junction structure and its influence on the characteristic parameters involved in the field-enhanced water dissociation phen…
Divalent Cations Reduce the pH Sensitivity of OmpF Channel Inducing the PKA Shift of Key Acidic Residues
In contrast to the highly-selective channels of neurophysiology employing mostly the exclusion mechanism, different factors account for the selectivity of large channels. Elucidation of these factors is essential for understanding the permeation mechanisms in ion channels and their regulation in vivo. The interaction between divalent cations and a protein channel, the bacterial porin OmpF, has been investigated paying attention to the channel selectivity and its dependence on the solution pH. Unlike the experiments performed in salts of monovalent cations, the channel is now practically insensitive to pH, being anion selective all over the pH range considered. Electrostatic calculations bas…
Ion selectivity and water dissociation in polymer bipolar membranes studied by membrane potential and current–voltage measurements
Abstract A polymer bipolar ion-exchange membrane consists of a layered structure involving one cation and one anion ion-exchange layer joined together in series. In this study, the ionic selectivity and water dissociation rate of six commercial bipolar membranes was evaluated from the measurements of the membrane potential in a concentration cell and the current–voltage curve in a four-point measuring cell. Bipolar membrane technology requires polymer membranes presenting high ion selectivities and water dissociation rates, and in this paper we have addressed the basic physico-chemical phenomena involved, both theoretically and experimentally. We have shown that the effects of the bipolar j…
Bone Turnover Markers and Potential Correlation with Outcomes in Patients with Genitourinary Cancer (Renal and Bladder) and Bone Metastasis (Results of the Tugamo Study)
ABSTRACT Background Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal related events (SRE), disease progression and death. The aim of the study was to determine the possible correlation between BTM, disease progression, SREs and death in patients with genitourinary cancer and bone metastases (BM) treated with zoledronic acid (ZA). Methods Observational, prospective, multicenter study. Patients with genitourinary cancer (prostate, renal, bladder) and BM were included. BTM determined were: carboxiterminal telopeptide of type I collagen (β-CTX) and bone specific alkaline phosphatase (BALP) by ELISA (immunoenzymatic assay, IDS UK), and aminoterminal pro…
Model calculations of ion transport against its concentration gradient when the driving force is a pH difference across a charged membrane
Model calculations of the steady-state ion transport against its external concentration gradient when the driving force of this transport is a pH difference across a charged membrane are presented. We have solved numerically the exact Nernst-Planck equations without any additional simplifying approximation, such as the Goldman constant field assumption within the membrane. The validity of this assumption for a broad range of pH values, and salt and membrane fixed charge concentrations was analyzed critically. The membrane characteristics studied are the ionic fluxes and the membrane potential. Special attention is paid to the physical mechanism which leads to the ion transport against the c…
Synthetic nanopores with fixed charges: An electrodiffusion model for ionic transport
Synthetic nanopores with fixed charges exhibit ionic equilibrium and transport properties that resemble those displayed by biological ion channels. We present an electrodiffusion model based on the Nernst-Planck flux equations, which allows for a qualitative description of the steady state ionic transport through a nanopore when the membrane fixed charges and all mobile carriers (including the water ions) are properly taken into account. In particular, we study the current-voltage curve, the electrical conductance, the reversal potential (a measure of the nanopore ionic selectivity), as well as the flux inhibition by protons and divalent cations in the nanopore. The model clearly shows how …
Modeling of Amino Acid Electrodiffusion through Fixed Charge Membranes
Abstract We study theoretically the electrodiffusion of amino acids through fixed charge membranes, calculating the ionic fractions of the amino acid in the membrane as well as its total flux as a function of the relevant experimental parameters (amino acid concentration, salt concentration, and pH of the external solution; membrane fixed charge concentration; and amino acid membrane/solution partition coefficients) under different experimental conditions (symport vs antiport transport, uphill transport, etc.). The theoretical approach employed is based on the Nernst–Planck flux equations in the (Goldman) constant electric field assumption and considers all the species present in the system…
The spanish banks in face of the corporate social responsibility Standards: previous analysis of the financial crisis
Transparency of information in the field of CSR (Corporate Social Responsibility) is common to various standards. In recent years there has been a proliferation of standards and models for the formalization of CSR strategies. The objective is to assess the degree of implementation of standards of normalization. The analysis was conducted with data from the year 2008, coinciding with the first signs of the financial crisis, serving as a reference point to analyze the effect of the crisis. The field work was conducted using a survey answered by 57 Spanish credit institutions. We found a low degree of implementation of standards. The GRI (Global Reporting Initiative) and the ISO 14001 stood ou…
Entropy–enthalpy compensation at the single protein level: pH sensing in the bacterial channel OmpF
The pH sensing mechanism of the OmpF channel operates via ligand modification: increasing acidity induces the replacement of cations with protons in critical binding sites decreasing the channel conductance. Aside from the change in enthalpy associated with the binding, there is also a change in the microscopic arrangements of ligands, receptors and the surrounding solvent. We show that the pH-modulation of the single channel conduction involves small free energy changes because large enthalpic and entropic contributions change in opposite ways, demonstrating an approximate enthalpy–entropy compensation for different salts and concentrations. We wish to acknowledge the support from the Span…