Changes In Proton Concentration Research Articles

Ultralow Power, Cleft Size-Adjustable and pH-Sensitive Hyaluronic Acid (HA) Biodevices for Acid-Sensing Ion Channels Emulation.

The burgeoning implantable biodevices have unlocked new frontiers in healthcare, promising personalized monitoring strategies tailored to specific needs. Herein, hyaluronic acid (HA) is harnessed to create fully biocompatible, acidity-sensitivity and cleft-adjustable neuromorphic devices. These HA-biodevices exhibit remarkable sensitivity to pH variations, effectively mimicking biological acid-sensing ion channels (ASICs) through protonation reactions between electronegative atoms and hydrogen ions, even at ultralow driving voltage (5mV). They can monitor joint cartilage acidity by tracking changes in proton concentration and successfully diagnose the onset of arthritis. Furthermore, by adjusting the synaptic device's cleft distance, which determines responsiveness, power efficiency and plasticity, HA-based neuromorphic devices can be tailored to meet the unique demands of various implantation sites, providing both high-sensitivity and low-heat dissipation, thus broadening their application scopes. Moreover, the HA-biodevices maintain stable performance across various bending degrees, up to a curvature radius of 7.5mm, with flexibility and deformation resilience enabling installation on joints of varying curvatures. The combination of all-biocompatibility, high sensitivity, low heat dissipation, ultralow low power (2 pW), and extraordinary deformation tolerance paves the way for the development of versatile, multipurpose medical monitoring devices with immense potential in the field of healthcare.

Basal lamina: A novel pH regulator at the neuromuscular junction.

Proton concentration can change within the cleft during synaptic activity due to vesicular release and Ca2+ extrusion from cellular compartments. These changes within the synaptic cleft can impact neural activity by proton-dependent modulation of ion channel function. The pH transient differs in magnitude and direction between synapses, requiring different synapse types to be measured to generate a complete understanding of this mechanism and its impacts on physiology. With a focus on the mouse neuromuscular junction (NMJ), the recently published "Postsynaptic Calcium Extrusion at the Mouse Neuromuscular Junction Alkalinizes the Synaptic Cleft" measured synaptic cleft pH at a cholinergic synapse and found a biphasic pH transient. The study demonstrated that the changes in proton concentration found were due to postsynaptic signaling when measuring pH at the muscle membrane, despite the expectation of a presynaptic contribution. This result suggests a diffusional barrier within the NMJ isolates pH transients to presynaptic versus postsynaptic compartments. Generating a Donnan equilibrium that impacts protons, evidence suggests the basal lamina may be a key regulator of pH at the NMJ. Exploring synaptic pH, proton regulating factors, and downstream pH transient effects at presynaptic versus postsynaptic membranes may lead to new insight for a variety of diseases.

The role of the SARS-CoV-2 envelope protein as a pH-dependent cation channel.

The role of the SARS-CoV-2 envelope protein as a pH-dependent cation channel.

Improving Chemo-Mechanical Stability of Proton-Conducting Perovskites

The superior ionic conductivity of selected proton-conducting perovskites enables development of intermediate temperature electrochemical devices, such as solid oxide fuel/electrolysis cells, gas separation membranes, and electrochemical reactors. The lower operating temperature, compared to those of most oxide ion-conductors, can benefit the durability of the devices, as most degradation mechanisms are thermally activated. On the other hand, the chemical strains associated with hydration/dehydration during processing or operation can be considerably larger than those seen in their oxide ion-conducting counterparts during oxygen loss/gain. There is therefore a significant need to develop proton conductors with lower coefficients of chemical expansion (CCE), which is the chemical strain normalized to the change in defect (proton) concentration. Since design principles for engineering CCEs are not well developed, we have previously been investigating the role of various structural and chemical features, such as size of the oxygen vacancy and charge localization.In this presentation, I will focus on our more recent work investigating the role of octahedral distortions and deviations away from the perfect cubic perovskite structure. By substituting differently sized isovalent cations on the A- and B-site of perovskites, it is possible to engineer the tolerance factor to vary the symmetry and distortions. We have therefore synthesized a series of (Ba,Sr)(Zr,Ce)0.9Y0.1O3-x perovskites with gradually varying tolerance factor. To measure hydration strains, isothermal in situ X-ray diffraction and dilatometry were performed at temperature points in the range ~360-680 °C, in varying humidities. To evaluate the corresponding changes in proton concentration, isothermal thermogravimetric analysis was applied under identical conditions; an intermediate, constant oxygen partial pressure was chosen to avoid the possibility of any simultaneous redox reactions contributing significantly to mass changes and strains. The combined results show that by diminishing the perovskite tolerance factor in this family of zirconate/cerate proton conductors, the coefficient of chemical expansion can be lowered by 500%. Further in situ X-ray diffraction analysis of powder vs. bulk samples, and density functional theory simulations of single crystals, have revealed that there are both crystal chemical and microstructural contributions to the trend seen. The results show that inducing octahedral rotations and lowering symmetry, by altering the cation radius ratio, is an effective route to increase chemo-mechanical stability by lowering CCEs.

Multidimensional Tunability of Nucleic Acids Enables Sensing over Unknown Backgrounds.

A longstanding challenge in quantitative analysis is the relationship between a sensor's dynamic range and a background: the response range must align with the target's background value. If this condition is not met, a reliable measurement is impossible. The requirement is especially critical for sensing systems displaying sharp responses. In this work, we have solved the problem of response range/background misalignment via design of sensing systems that adjust their response to actual unknown backgrounds. The sensing systems are based on nucleic acid scaffolds: due to an intrinsic trait of multidimensional tunability, the sensors can assess the actual background and adjust response range accordingly. We established a general methodology and demonstrated, as a proof-of-concept, a practically meaningful example of detecting very small changes in proton concentrations over unknown aqueous backgrounds using a DNA i-motif sensor. Owing to multidimensional tunability of a DNA i-motif, this sensor could reliably measure changes in proton concentration that are 3 orders of magnitude below currently available methodologies.

Understanding of proton induced synaptic behaviors in three-terminal synapse device for neuromorphic systems

In this study, we investigate a proton-based three-terminal (3-T) synapse device to realize linear weight-update and I–V linearity characteristics for neuromorphic systems. The conductance states of the 3-T synapse device can be controlled by modulating the proton concentration in the WOx channel. Therefore, we estimate the dynamic change of proton concentration in the channel region, which directly affects synaptic behaviors. Our findings indicate that the supply of an excess number of protons from the SiO2–H electrolyte and low proton diffusivity in the WOx channel result in asymmetric and non-linear weight-update characteristics. In addition, though the linear I–V characteristics can be obtained using non-stoichiometric WOx, we observe that significant oxygen deficiency in the channel region increases the operating current levels. Thus, based on this information, we introduce optimized conditions of each component in the 3-T synapse device and shape of the gate voltage pulses. As a result, an excellent classification accuracy is achieved using linear weight-update and I–V linearity characteristics under optimized device and pulse conditions.

Design of pH-responsive gold nanoparticles in oncology

Gold nanoparticles (AuNPs) hold promising applications in many fields such as electronics, optics and catalysis. In the past decades, there has been a growing interest for their application in medicine, in particular in nano-oncology as contrast agents, drug delivery vehicles or for diagnosis. Once injected intravenously and thanks to their small size, the AuNPs can circulate in the whole body via the blood stream and reach easily the tumour. However, what makes them very attractive for cancer treatment is their ability to distinguish healthy cells from cancer cells. While the current anticancer agents lack specific targeting, AuNPs, with their targeting efficiency, will enable the use of lower amount of drugs with all the positive aspects for the health of the patient. Additionally, their optical properties give them the ability to be used in imaging as an incredibly powerful contrast agent. For these reasons, they are believed to be one of the tools that, in the future, will enable to considerably increase the efficiency of cancer treatments by simultaneously imaging the tumour and treat it. They constitute an ideal theranostic drug delivery platform, in other words a unique combination of diagnostics and therapy. Many researches focus on the engineering of the nanoparticle surface in order to increase their biocompatibility and enable their further conjugation with bioactive ligands such as drugs, targeting or imaging agents for the design of multifunctional platforms. pH responsiveness, the ability to change properties with a change of proton concentration, is a remarkable asset for drug delivery carrier. Indeed, it has been demonstrated that cancer cells show very particular pHs in their environment: extracellular as well as intracellular. This characteristic has been exploited to create a more specific and efficient way to treat cancer. The present review focuses on the design of pH responsive AuNPs and particularly on the advantages and the potential applications of such hybrid nanomaterials in oncology.

Advances in Use of Capsule-Based Fluorescent Sensors for Measuring Acidification of Endocytic Compartments in Cells with Altered Expression of V-ATPase Subunit V1G1.

Acidification of eukaryotic cell compartments is accomplished by vacuolar H+-ATPases (V-ATPases), large multisubunit complexes able to pump protons into the lumen of organelles or in the extracellular medium. V-ATPases are involved in a number of physiological cellular processes, and thus regulation of V-ATPase activity is of crucial importance for the cell. Indeed, dysfunction of V-ATPase or alterations of acidification have been recently recognized as key factors in a variety of human diseases. In this study, we applied capsule-based pH sensors and a real-time tracking method for investigating the role of the V1G1 subunit of V-ATPases in regulating the activity of the proton pump. We first constructed stable cell lines overexpressing or silencing the subunit V1G1. Second, we used fluorescent capsule-based pH sensors to monitor acidification before and during internalization by modified and control living cells. By using a simple real-time method for tracking capsule internalization, we were able to identify different capsule acidification levels with respect to each analyzed cell and to establish the kinetics for each. The intracellular pH measurements indicate a delay in acidification in either V1G1-overexpressing or V1G1-silenced cells compared to controls. Finally, in an independent set of experiments, we applied transmission electron microscopy and confocal fluorescence microscopy to further investigate the internalization of the capsules. Both analyses confirm that capsules are engulfed in acidic vesicular structures in modified and control cell lines. The use of capsule-based pH sensors allowed demonstration of the importance of the V1G1 subunit in V-ATPase activity concerning intravesicular acidification. We believe that the combined use of these pH-sensor system and such a real-time method for tracking their internalization path would contribute to systematically measure the proton concentration changes inside the endocytic compartments in various cell systems. This approach would provide fundamental information regarding molecular mechanisms and factors that regulate intracellular acidification, vesicular trafficking, and cytoskeletal reorganizations.

In situ Raman spectroscopic measurement of near-surface proton concentration changes during electrochemical reactions.

We report a simple in situ Raman spectroscopic measurement of near-surface proton concentration changes at commercial Pt black nanoparticle surfaces using the well-known methanol oxidation, oxygen reduction, Pt oxidation and reduction reactions as the representative illustrating examples.

(Invited) Proton Transport in Inorganic Phosphates

The proton conduction mechanism of well-characterized SnP2O7 and Sn1-xInxP2O7 materials was investigated using AC impedance spectroscopy and inelastic neutron scattering. Samples with minimal amounts of excess phosphate do not possess appreciable conductivity at room temperature. Indium doping appears to increase the high temperature proton conductivity of the materials. Inelastic neutron scattering data indicates that no appreciable changes in proton concentration occur between hydrated and dehydrated samples of SnP2O7 while changes in proton vibrational mode amplitudes occur with indium doping, or upon hydration, of samples that contain excess phosphate.

Biogeochemical context impacts seawater pH changes resulting from atmospheric sulfur and nitrogen deposition

AbstractSeawater acidification can be induced both by absorption of atmospheric carbon dioxide (CO2) and by atmospheric deposition of sulfur and nitrogen oxides and ammonia. Their relative significance, interplay, and dependency on water column biogeochemistry are not well understood. Using a simple biogeochemical model we show that the initial conditions of coastal systems are not only relevant for CO2‐induced acidification but also for additional acidification due to atmospheric acid deposition. Coastal areas undersaturated with respect to CO2 are most vulnerable to CO2‐induced acidification but are relatively least affected by additional atmospheric deposition‐induced acidification. In contrast, the pH of CO2‐supersaturated systems is most sensitive to atmospheric deposition. The projected increment in atmospheric CO2 by 2100 will increase the sensitivity of coastal systems to atmospheric deposition‐induced acidification by up to a factor 4, but the additional annual change in proton concentration is at most 28%.

Fluorescence indicative pH drop in sonication

Sonication induces complex chemical and physical phenomena in solution, which attracted great attentions to discover the mechanisms behind these phenomena. One of these phenomena is the pH drop in sonication, which was usually attributed to the formation of nitrate and nitrite acid in sonication. However, the pH drop detected by electrodes was questioned since the sonication could enhance proton transfer on the surface of pH electrode, resulting in a false pH drop. Therefore, it is necessary to initiate a tour study on this issue. In this paper, we firstly investigate two new factors, namely CO2 dissolution and temperature, which have the possibility to induce the pH drop in sonication. The results demonstrate that both factors play a minor role on the pH drop. Then we employ pH sensitive dyes to replace the questioned pH electrode to detect the change of proton concentration in sonication. The results indicate that the pH drop is accompanied with the protonation of fluorescein, indicating production of hydrogen ions in sonication. The quantitative analysis of proton production suggests that the pH drop in sonication is mainly caused by the formation of hydrogen ions, which clarify the reason for the pH drop in sonication.

The numerical simulation of dynamic performance in the vanadium flow battery

A simple dynamic model, taking into account the change of proton concentration and dynamic diffusion of vanadium ions, is developed to predict the performances of the vanadium flow battery (VFB). The model is verified via the cycle experiment on the single cell battery assembled with Nafion 115 membrane. The simulated voltage of the VFB single cell during a charge-discharge cycle is in agreement with the experimental results. The efficiency and capacity vs. number of cycles evaluated by this model agree quite well with the experimental data as well. Comparing with the model neglecting the proton concentration change and dynamic diffusion of vanadium ions, the presented model can better forecast the performances of the VFB.

Regulation of electron-transport pathways in cells of Chlamydomonas reinhardtii under stress conditions

The kinetics of interactions between electron-transport pathways in the thylakoid membrane was examined. A mathematical model was proposed to describe the kinetics of redox transitions in photosystem II, proton concentration changes in the chloroplast stroma, and the plastoquinone pool reduction due to photosynthetic and chlororespiratory pathways. A kinetic mechanism is considered that redirects electron flows between photosynthetic and chlororespiratory pathways in response to the increased NADPH content under mineral deficiency. According to the simulation model, the electron transport flows via different routes are switched over in a stepwise manner. The results of numerical simulations are qualitatively consistent with experimental data for Chlamydomonas reinhardtii cells subjected to mineral deprivation.

Dual-lifetime referencing (DLR): a powerful method for on-line measurement of internal pH in carrier-bound immobilized biocatalysts

BackgroundIndustrial-scale biocatalytic synthesis of fine chemicals occurs preferentially as continuous processes employing immobilized enzymes on insoluble porous carriers. Diffusional effects in these systems often create substrate and product concentration gradients between bulk liquid and the carrier. Moreover, some widely-used biotransformation processes induce changes in proton concentration. Unlike the bulk pH, which is usually controlled at a suitable value, the intraparticle pH of immobilized enzymes may deviate significantly from its activity and stability optima. The magnitude of the resulting pH gradient depends on the ratio of characteristic times for enzymatic reaction and on mass transfer (the latter is strongly influenced by geometrical features of the porous carrier). Design and selection of optimally performing enzyme immobilizates would therefore benefit largely from experimental studies of the intraparticle pH environment. Here, a simple and non-invasive method based on dual-lifetime referencing (DLR) for pH determination in immobilized enzymes is introduced. The technique is applicable to other systems in which particles are kept in suspension by agitation.ResultsThe DLR method employs fluorescein as pH-sensitive luminophore and Ru(II) tris(4,7-diphenyl-1,10-phenantroline), abbreviated Ru(dpp), as the reference luminophore. Luminescence intensities of the two luminophores are converted into an overall phase shift suitable for pH determination in the range 5.0-8.0. Sepabeads EC-EP were labeled by physically incorporating lipophilic variants of the two luminophores into their polymeric matrix. These beads were employed as carriers for immobilization of cephalosporin C amidase (a model enzyme of industrial relevance). The luminophores did not interfere with the enzyme immobilization characteristics. Analytical intraparticle pH determination was optimized for sensitivity, reproducibility and signal stability under conditions of continuous measurement. During hydrolysis of cephalosporin C by the immobilizate in a stirred reactor with bulk pH maintained at 8.0, the intraparticle pH dropped initially by about 1 pH unit and gradually returned to the bulk pH, reflecting the depletion of substrate from solution. These results support measurement of intraparticle pH as a potential analytical processing tool for proton-forming/consuming biotransformations catalyzed by carrier-bound immobilized enzymes.ConclusionsFluorescein and Ru(dpp) constitute a useful pair of luminophores in by DLR-based intraparticle pH monitoring. The pH range accessible by the chosen DLR system overlaps favorably with the pH ranges at which enzymes are optimally active and stable. DLR removes the restriction of working with static immobilized enzyme particles, enabling suspensions of particles to be characterized also. The pH gradient developed between particle and bulk liquid during reaction steady state is an important carrier selection parameter for enzyme immobilization and optimization of biocatalytic conversion processes. Determination of this parameter was rendered possible by the presented DLR method.

Proton feedback mediates the cascade of color-opponent signals onto H3 horizontal cells in goldfish retina

It has been postulated that horizontal cells (HCs) send feedback signals onto cones via a proton feedback mechanism, which generates the center-surround receptive field of bipolar cells, and color-opponent signals in many non-mammalian vertebrates. Here we used a strong pH buffer, HEPES, to reduce extracellular proton concentration changes and so determine whether protons mediate color-opponent signals in goldfish H3 (triphasic) HCs. Superfusion with 10mM HEPES-fortified saline elicited depolarization of H3 HCs’ dark membrane potential and enhanced hyperpolarizing responses to blue stimuli, but suppressed both depolarization by yellow and orange and hyperpolarization by red stimuli. The response components suppressed by HEPES resembled the inverse of spectral responses of H2 (biphasic) HCs. These results are consistent with the Stell–Lightfoot cascade model, in which the HEPES-suppressed component of H3 HCs was calculated using light responses recorded experimentally in H1 (monophasic) and H2 HCs. Selective suppression of long- or long-+middle-wavelength cone signals by long-wavelength background enhanced the responses to short-wavelength stimuli. These results suggest that HEPES inhibited color opponent signals in H3 HCs, in which the source of opponent-color signals is primarily a feedback from H2 HCs and partly from H1 HCs onto short-wavelength cones, probably mediated by protons.

Separate Gating Mechanisms Mediate the Regulation of K2P Potassium Channel TASK-2 by Intra- and Extracellular pH

TASK-2 (KCNK5 or K(2P)5.1) is a background K(+) channel that is opened by extracellular alkalinization and plays a role in renal bicarbonate reabsorption and central chemoreception. Here, we demonstrate that in addition to its regulation by extracellular protons (pH(o)) TASK-2 is gated open by intracellular alkalinization. The following pieces of evidence suggest that the gating process controlled by intracellular pH (pH(i)) is independent from that under the command of pH(o). It was not possible to overcome closure by extracellular acidification by means of intracellular alkalinization. The mutant TASK-2-R224A that lacks sensitivity to pH(o) had normal pH(i)-dependent gating. Increasing extracellular K(+) concentration acid shifts pH(o) activity curve of TASK-2 yet did not affect pH(i) gating of TASK-2. pH(o) modulation of TASK-2 is voltage-dependent, whereas pH(i) gating was not altered by membrane potential. These results suggest that pH(o), which controls a selectivity filter external gate, and pH(i) act at different gating processes to open and close TASK-2 channels. We speculate that pH(i) regulates an inner gate. We demonstrate that neutralization of a lysine residue (Lys(245)) located at the C-terminal end of transmembrane domain 4 by mutation to alanine abolishes gating by pH(i). We postulate that this lysine acts as an intracellular pH sensor as its mutation to histidine acid-shifts the pH(i)-dependence curve of TASK-2 as expected from its lower pK(a). We conclude that intracellular pH, together with pH(o), is a critical determinant of TASK-2 activity and therefore of its physiological function.

Effects of polypyrrole modified electrode functionalization on potentiometric pH responses

Two functionalized polypyrrole films, poly(11-N-pyrrolylundecanoic) acid and poly(N-undecylpyrrole), were used as sensitive layers for pH sensors. The functionalized pyrrole monomers were first synthesized before carrying out their electropolymerization onto non-oxidizable electrodes. The deposits were characterized by SEM imaging, XPS and PM-IRRAS to study surface structure and composition. Poly(11-N-pyrrolylundecanoic) acid coating yielded very promising results as sensitive layer in pH sensors. Indeed, the potentiometric responses from pH 4.0 to 9.0 appeared linear, reversible, stable in time over a period of 1 month and highly selective for H + ions. This behavior was attributed to carboxylic acid groups which are sensitive to proton concentration changes. This was confirmed by the fact that poly(N-undecylpyrrole) film led to potentiometric responses being pH dependent only from pH 6.0 to 9.0 with low sensitivity. Poly(11-N-pyrrolylundecanoic) acid is thus promoted to be used as sensitive layer in pH sensors.

Efficient Approach to Determine the pKa of the Proton Release Complex in the Photocycle of Retinal Proteins

This work utilizes a photoelectrochemical approach to study the pH dependence of proton release and uptake in the photocycles of two retinal proteins, bacteriorhodopsin (BR) and archaerhodopsin 4 (AR4). By detecting photoinduced potentials that originate from the proton concentration changes (DeltaH(+)) generated by proteins near the indium tin oxide (ITO) electrode, we show that the kinetics of release and uptake can be followed in a broad pH range, and the pK(a) of the proton release complex (PRC) can be easily determined under different conditions. Nonoriented protein films were deposited on the electrode, and photovoltage in an electrochemical cell was detected after illumination with a green flash. The kinetics of proton release and uptake could be measured as light-induced decreases and increases of the photopotential. A kinetic analysis was performed, and a formula describing proton fluxes of wild-type BR and AR4 and D96N mutant of BR was derived. Three componentsfast proton release, slow proton release, and proton uptakewere found in the wild-type retinal proteins; two components, fast and slow proton releases, were found in the D96N mutant. The pH dependence of the fraction of fast release over the whole release was used to determine the pK(a) for proton release in the photocycles of these retinal proteins. Measurements were also performed in conventional buffer solutions and crown ether. The presence of buffer in 10-50 mM concentration did not abolish the light-induced signals, indicating that the electrode response is much less sensitive to buffers than pH-sensitive dyes in a suspension due to a higher protein/buffer ratio near the electrode. This feature enables us to study effects of chemicals with high buffer capacity, and significant effects of buffers and crown ether on proton pumping behaviors of retinal proteins were revealed. In comparison with the classic pH-sensitive dye approach, the photoelectrochemical approach is convenient and efficient for measurements of transient proton concentration changes (DeltaH(+)) generated by a proton pump and thus might be utilized as a powerful tool for the investigation of light-driven proton pumping mechanisms in a wide pH range.

PH-Dependent Interdomain Tethers of CD1b Regulate Its Antigen Capture

As CD1 proteins recycle between the cell surface and endosomes, they show altered receptiveness to lipid antigen loading. We hypothesized that changes in proton concentration encountered within distinct endosomal compartments influence the charge state of residues near the entrance to the CD1 groove and thereby control antigen loading. Molecular dynamic models identified flexible areas of the CD1b heavy chain in the superior and lateral walls of the A' pocket. In these same areas, residues that carry charge in a pH-dependent manner (D60, E62) were found to tether the rigid alpha1 helix to flexible areas of the alpha2 helix and the 50-60 loop. After disruption of these tethers with acid pH or mutation, we observed increased association and dissociation of lipids with CD1b and preferential presentation of antigens with bulky lipid tails. We propose that ionic tethers act as molecular switches that respond to pH fluxes during endosomal recycling and regulate the conformation of the CD1 heavy chain to control the size and rate of antigens captured.