Effect Of Charge Reversal Research Articles

Pickering Emulsions Stabilized by Polystyrene Particles Possessing Different Surface Groups.

Colloidal polystyrene (PS) latex particles in water can undergo interesting charge reversal in the presence of particular electrolytes. It is worth exploring the effect of charge reversal on the properties of Pickering emulsions they stabilize. Herein, emulsions stabilized by PS latex particles possessing different surface groups (sulfate, amidine, or carboxyl) were prepared in the presence of tetrapentylammonium bromide (TPeAB) or sodium thiocyanate (NaSCN) electrolytes. The effect of salt concentration on the charge of the particles and their colloid stability was measured. Emulsions were prepared from aqueous dispersions, and their type and stability were determined. The three-phase contact angle of particles at the planar oil–water interface was also measured using a gel trapping technique. It was found that the type of emulsion stabilized by latex particles is dominated by the hydrophobic PS portion on particle surfaces, although their surface charge is strongly affected by electrolyte addition. Preferred emulsions were always water-in-oil with dodecane, and charge reversal had little influence on the emulsion type and stability. However, transitional phase inversion of emulsions stabilized by carboxyl latex particles occurred on adding salt when the oil was a low-viscosity polydimethylsiloxane.

Role of charge-reversal in the hemo/immuno-compatibility of polycationic gene delivery systems

As an effective and well-recognized strategy used in many delivery systems, such as polycation gene vectors, charge reversal refers to the alternation of vector surface charge from negative (in blood circulation) to positive (in the targeted tissue) in response to specific stimuli to simultaneously satisfy the requirements of biocompatibility and targeting. Although charge reversal vectors are intended to avoid interactions with blood in their application, no overall or systematic investigation has been carried out to verify the role of charge reversal in the blood compatibility. Herein, we comprehensively mapped the effects of a typical charge-reversible polycation gene vector based on pH-responsive 2,3-dimethylmaleic anhydride (DMMA)-modified polyethylenimine (PEI)/pDNA complex in terms of blood components, coagulation function, and immune response as compared to conventional PEGylated modification. The in vitro and in vivo results displayed that charge-reversal modification significantly improves the PEI/pDNA-induced abnormal effect on vascular endothelial cells, platelet activation, clotting factor activity, fibrinogen polymerization, blood coagulation process, and pro-inflammatory cytokine expression. Unexpectedly, (PEI/pDNA)-DMMA induced the cytoskeleton impairment-mediated erythrocyte morphological alternation and complement activation even more than PEI/pDNA. Further, transcriptome sequencing demonstrated that the overexpression of pro-inflammatory cytokines was correlated with vector-induced differentially expressed gene number and mediated by inflammation-related signaling pathways (MAPK, NF-κB, Toll-like receptor, and JAK-STAT) activation. By comparison, charge-reversal modification improved the hemocompatibility to a greater extent than dose PEGylation except for erythrocyte rupture. Nevertheless, it is inferior to mPEG modification in terms of immunocompatibility. These findings provide comprehensive insights to understand the molecular mechanisms of the effects of charge reversal on blood components and their function and to provide valuable information for its potential applications from laboratory to clinic. Statement of SignificanceThe seemingly revolutionary charge reversal strategy has been believed to possess stealth character with negative charge eluding interaction with blood components during circulation. However to date, no overall or systematic investigation has been carried out to verify the role of charge-reversal on the blood/immune compatibility, which impede their development from laboratory to bedside. Therefore, we comprehensively mapped the effects of a typical charge-reversible polycationic gene vector on blood components (vascular endothelial cell, platelet, clotting factors, fibrinogen, RBCs and coagulation function) and immune response (complement and pro-inflammatory cytokines) at cellular and molecular level in comparison to PEGylation modification. These findings help to elucidate the molecular mechanisms for the effects of charge-reversal on blood components and functions, and provide valuable information for the possible application in clinical settings.

Nanopore charge inversion and current-voltage curves in mixtures of asymmetric electrolytes

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 with monovalent potassium (K+) and divalent Mg2+ ions at biologically relevant concentrations. It is found that small concentrations of multivalent ions can modulate the nanopore rectification and the transport of other majority ions in the solution. We study also the kinetics of the nanopore electrical recovery when the electrolyte solutions bathing the single-pore membrane are changed and show the hysteretic effects observed in the I–V curves. Finally, we describe the hysteresis observed in the I–V curves of CaCl2, MgCl2, and BaCl2 and mixtures. We also give a qualitative description of the effects of charge reversal on the pore rectification using the Nernst-Planck flux equations for multivalent ion mixtures.

Memory and nonlinear transport effects in charging–discharging of a supercapacitor

We report on the results of analysis of the kinetics of charge–discharge current of Panasonic supercapacitors in a wide range of time from 10–1 to 104 s. The non-Debye behavior of relaxation observed earlier by us and other authors is confirmed experimentally, and the influence of the supercapacitor charging regime on this process for various previous histories (values of applied voltage, charging time, and load resistance) is analyzed. The results are compared with available experimental data for paper–oil and electrolytic capacitors and with the results of calculations in the linear response model. It is found that in contrast to conventional capacitors, the response of the supercapacitor under investigation to variations of the charging regime does not match the linear response model. The relation of this nonlinearity to processes in the double electric layer, the morphology of the porous electrode, and the effect of charge reversal in pores is considered.

Effects of Ca(OH)2 assisted aluminum sulfate coagulation on the removal of humic acid and the formation potentials of tri-halomethanes and haloacetic acids in chlorination

The effects of addition of calcium hydroxide on aluminum sulphate (or alum) coagulation for removal of natural organic matter (NOM) and its subsequent effect on the formation potentials of two major types of regulated disinfection byproducts (DBPs), haloacetic acids (HAAs) and trihalomethanes (THMs), have been examined. The results revealed several noteworthy phenomena. At the optimal coagulation pH (i.e. 6), the coagulation behavior of NOM water solutions versus alum dose, showed large variation and a consequent great change in the formation potentials of the DBPs at certain coagulant doses. However, with addition of a relatively small amount of Ca(OH)2, although the zeta potential of coagulated flocs remained almost the same, NOM removal became more consistent with alum dose. Importantly, also the detrimental effect of charge reversal on NOM removal at the low coagulant dose disappeared. This resulted in a steady decrease in the formation potentials of DBPs as a function of the coagulant dose. Moreover, the addition of Ca(OH)2 broadened the pH range of alum coagulation and promoted further reduction of the formation potentials of the DBPs. The enhancement effects of Ca(OH)2 assisted alum coagulation are especially pronounced at pH 7 and 8. Finally, synchronous fluorescence spectra showed that the reduction in DBPs formation potential by Ca(OH)2-assisted alum coagulation was connected to an enhanced removal of small hydrophobic and hydrophilic HA molecules. Ca(OH)2-assistance of alum coagulation appeared to increase substantially the removal of the hydrophilic HA fraction responsible for HAAs formation, prompting further reduction of HAA formation potentials.

The Pore of the Voltage-Gated Proton Channel

In classical tetrameric voltage-gated ion channels four voltage-sensing domains (VSDs), one from each subunit, control one ion permeation pathway formed by four pore domains. The human Hv1 proton channel has a different architecture, containinga VSD, but lacking a pore domain. Since its location is not known, we searched for the Hv permeation pathway. We find that mutation of the S4 segment's third arginine R211 (R3) compromises proton selectivity, enabling conduction of a metal cation and even of the large organic cation guanidinium, reminiscent of Shaker's omega pore. In the open state, R3 appears to interact with an aspartate (D112) that is situated in the middle of S1 and is unique to Hv channels. The double mutation of both residues further compromises cation selectivity. We propose that membrane depolarization reversibly positions R3 next to D112 inthe transmembrane VSD to form the ion selectivity filter in the channel's open conformation.

A Novel Binding Site for the Human Insulin-like Growth Factor-II (IGF-II)/Mannose 6-Phosphate Receptor on IGF-II

The mammalian insulin-like growth factor (IGF)-II/cation-independent mannose 6-phosphate receptor (IGF2R) binds IGF-II with high affinity. By targeting IGF-II to lysosomal degradation, it plays a role in the maintenance of correct IGF-II levels in the circulation and in target tissues. Loss of IGF2R function is associated with tumor progression; therefore, the IGF2R is often referred to as a tumor suppressor. The interaction between IGF2R and IGF-II involves domains 11 and 13 of the 15 extracellular domains of the receptor. Recently, a hydrophobic binding region was identified on domain 11 of the IGF2R. In contrast, relatively little is known about the residues of IGF-II that are involved in IGF2R binding and the determinants of IGF2R specificity for IGF-II over the structurally related IGF-I. Using a series of novel IGF-II analogues and surface plasmon resonance assays, this study revealed a novel binding surface on IGF-II critical for IGF2R binding. The hydrophobic residues Phe(19) and Leu(53) are critical for IGF2R binding, as are residues Thr(16) and Asp(52). Furthermore, Thr(16) was identified as playing a major role in determining why IGF-II, but not IGF-I, binds with high affinity to the IGF2R.

Clay charge reversal effects on aqueous polymer sorption on lateritic soils

The effects of charge reversal about the measured point of zero charge (pH 0 ≈ 5.2) of untreated and treated Sete Lagoas lateritic soil of Brazil on aqueous polymer sorption was investigated. The polymers are anionic sodium carboxymethyl cellulose (CMCA), nonionic polyethylene oxide (PEO), and cationic polyacrylamide (PAM). They were prepared at aqueous concentrations and pH ranges of 0.1–2.0 g l −1 and 2–9, respectively. Soil treatment involved the removal of iron oxides by treatment with dithionate–bicarbonate–citrate. Batch sorption test results show that the presence of iron oxides in lateritic soil tends to suppress sorption of CMCA (especially at pH = pH 0) and PEO (for the whole pH range) but has uncertain effects on cationic PAM sorption. CMCA sorption on the untreated soil improves on either side of pH 0, in direct proportionality to solution concentration, except at pH < 4.0, where disassociation of the polymer molecules may decrease sorption energy. Increase in the sorption of non-cationic polymers (CMCA and PEO) at pH > pH 0 is attributable to dispersion of clay, cation bridging and polymer molecular reconfiguration. For cationic PAM, electrostatic bonding to negatively charged soil particle surfaces accounts for the sorption increase. For treated soil samples, polymer sorption pattern is similar to those expected for the montmorillonitic clayey soils of temperate zones. These results indicate that the pH 0 of lateritic soils, within the regime that exists in the field, should be considered in assessing the potential effectiveness of polymer dust suppressants for tropical lateritic soils.

Electrostatic Contributions to T4 Lysozyme Stability: Solvent-Exposed Charges versus Semi-Buried Salt Bridges

We carried our Poisson-Boltzmann (PB) calculations for the effects of charge reversal at five exposed sites (K16E, R119E, K135E, K147E, and R154E) and charge neutralization and proton titration of the H31-D70 semi-buried salt bridge on the stability of T4 lysozyme. Instead of the widely used solvent-exclusion (SE) surface, we used the van der Waals (vdW) surface as the boundary between the protein and solvent dielectrics (a protocol established in our earlier study on charge mutations in barnase). By including residual charge-charge interactions in the unfolded state, the five charge reversal mutations were found to have ΔΔ G unfold from −1.6 to 1.3 kcal/mol. This indicates that the variable effects of charge reversal observed by Matthews and co-workers are not unexpected. The H31N, D70N, and H31N/D70N mutations were found to destabilize the protein by 2.9, 1.3, and 1.6 kcal/mol, and the pK a values of H31 and D70 were shifted to 9.4 and 0.6, respectively. These results are in good accord with experimental data of Dahlquist and co-workers. In contrast, if the SE surface were used, the H31N/D70N mutant would be more stable than the wild-type protein by 1.3 kcal/mol. From these and additional results for 27 charge mutations on five other proteins, we conclude that 1) the popular view that electrostatic interactions are generally destabilizing may have been based on overestimated desolvation cost as a result of using the SE surface as the dielectric boundary; and 2) while solvent-exposed charges may not reliably contribute to protein stability, semi-buried salt bridges can provide significant stabilization.

About the TATB assumption: effect of charge reversal on transfer of large spherical ions from aqueous to non-aqueous solvents and on their interfacial behaviour

We present a molecular dynamics study of the solvation properties of large spherical ions S+ and S− of same size, in water, chloroform and acetonitrile solutions, and at a water–chloroform interface. According to the “extrathermodynamic” TATB hypothesis, such ions have identical free energies of transfer from water to any solvent. We find that this is not the case, because S− interacts better than S+ with water (by about 20kcalmol−1), while S+ is better solvated by acetonitrile (by about 2kcalmol−1) and chloroform (about 8kcalmol−1) solvents. The importance of “long-range” electrostatic interactions on the charge discrimination by solvent is demonstrated by the comparison of standard vs corrected methods to calculate: (i) the electrostatic potential at the centre of the solute; (ii) the interaction energies between the ions and the solvents; and (iii) the free energies of charging the neutral sphere S0 to S+ and S−, respectively. These conclusions are obtained with several solvent models and simulation conditions. The question of ion pairing for the S+S−, S+Cl− and S−Na+ pairs is also examined in the three solvents. Finally, simulations at a liquid–liquid water–chloroform interface represented explicitly, show that S+ and S− are highly surface active, although they do not possess, like classical surfactants, an amphiphilic topology. Adsorption at the interface is found with different methodologies and at different ion concentrations. These results are important in the context of the “TATB hypothesis”, and for our understanding of solvation of large hydrophobic ions in pure liquids or in heterogeneous liquid environments.

Studies on the interaction of charge-reversed emulsions with the reticuloendothelial system

The effect of charge reversal on the uptake of fat emulsions by the reticuloendothelial (RE) system has been assessed by in vitro and in vivo methods. Emulsions stabilized by egg lecithin were charge reversed from negative to positive by added calcium ions that are adsorbed at the emulsion surface. The interaction of positively charged emulsion droplets with rat Kupffer cells was not significantly different to that found with negatively charged emulsion droplets. In all cases the measured uptake was low. Blockade of the reticuloendothelial system by infused fat emulsion was evaluated in vivo using a rabbit model. RE function was quantified by means of a probe in the form of radiolabelled albumin microspheres together with gamma scintigraphy. The kinetics of uptake of the probe into the liver/spleen regions and organ analysis showed that there were no differences between conventional and charge reversed systems. The extent of RE blockade was small in all cases.