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1.
Otolaryngol Clin North Am ; 56(1): 125-136, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36266104

RESUMO

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR channel is responsible for the transport of the anions (chloride and bicarbonate) across airway epithelia. Patients with CF have thick mucus, disrupted mucociliary transport, and chronic bacterial infections in the upper and lower airways. In this article, the pathophysiology of CFTR dysfunction and its impact on the united airway are reviewed as well as the treatment strategies for patients with chronic rhinosinusitis-related CF and acquired CFTR dysfunction.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/genética , Depuração Mucociliar , Transporte de Íons , Cloretos/metabolismo
2.
Bioconjug Chem ; 33(11): 2143-2148, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36345049

RESUMO

Synthetic calcium transporters are few despite their potential biological significance. Herein, we report small alanine-derived peptides containing pyridyl-triazole motifs for inducing calcium selectivity. The peptides are decorated with hydrophobic alkyl chains to facilitate membrane insertion. The most efficient peptide scaffold has an EC50 value of 0.09 mol % and functions as a calcium carrier.


Assuntos
Cálcio , Peptídeos , Ionóforos , Cálcio/metabolismo , Peptídeos/química , Transporte Biológico , Transporte de Íons
3.
Curr Top Membr ; 90: 1-11, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36368870

RESUMO

Cardiovascular disease is on the rise, partially due to the continued increase in metabolic syndrome. Advances in basic research on vascular ion transport have the potential to provide targets for therapeutic interventions. Vascular specificity, which includes different vascular beds having different characteristics and the macro- vs. microvasculature, is a vitally important variable in characterization of ion transport. At the cellular level, targeted fluorescent biosensors for Ca2+, super-resolution microscopy, and organelle patch clamp electrophysiology enable more detailed studies. The "MetS/diabetes milieu" includes increased and decreased insulin, and increased glucose, increased LDL/HDL cholesterol and triglycerides, and increased blood pressure. The duration and severity of MetS/diabetes components certainly affect the vascular phenotype and ion transport and membrane interactions. A combination of in vivo animal models and in vitro cell models to study ion transport in MetS/diabetes conditions is optimal. Gene editing and selective pharmacological tools should be used after or in conjunction with characterization of ion transport in vascular health and disease phenotypes. This is critical to determining the causal role of Ca2+ signaling in modulation of vascular phenotype. The ion transport and membrane interactions that are measured are typically only a snapshot in time in these dynamic processes occurring over the progression of health and disease. It is imperative that this concept be considered in the planning of long-term studies of vascular disease, ion transport experiments, and interpretation of the data. Future directions for our contributors' research will advance the field.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Síndrome Metabólica , Animais , Transporte de Íons
4.
J Cardiothorac Surg ; 17(1): 284, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348498

RESUMO

BACKGROUND: Uniport video-assisted thoracoscopic surgery (VATS) has been applied widely for the treatment of lung cancer in recent years. Some studies have reported that uniport VATS might provide better outcomes than multiport VATS. However, the perioperative outcomes of uniport VATS compared with two-port and three-port VATS, respectively, have yet to be studied at a comprehensive scale. This meta-analysis study compares the perioperative efficacy among uniport, two-port, and three-port VATS. METHODS: We searched studies published before October 1, 2019, by using Web of Science databases, Ovid Medline, Embase, and PubMed. Studies that compared uniport VATS with two-port or three-port VATS for patients with lung cancer were included. Operative time, perioperative blood loss, number of lymph nodes retrieved, conversion rate, duration of postoperative chest tube drainage, length of hospital stay (LoS), visual analogue pain scores on postoperative day (POD) 1 and POD 3, and overall morbidity were evaluated. RESULTS: Sixteen studies that compared uniport VATS with two-port or three-port VATS in the treatment of lung cancer were included. Uniport VATS showed less blood loss, a shorter duration of postoperative drainage and a lower visual analogue pain score on POD 3 than two-port VATS; it showed a shorter duration of postoperative drainage, a shorter LoS, and lower visual analogue pain scores on POD 1 and POD 3 than three-port VATS. There were no significant differences in the number of lymph nodes retrieved, operative time, conversion rate, and overall morbidity rate when comparing uniport VATS with two-port VATS or three-port VATS. CONCLUSIONS: Uniport VATS might provide better perioperative outcomes than either two-port or three-port VATS in lung cancer treatment.


Assuntos
Neoplasias Pulmonares , Cirurgia Torácica Vídeoassistida , Humanos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Duração da Cirurgia , Transporte de Íons , Dor
5.
Sci Rep ; 12(1): 19110, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351955

RESUMO

Premature cardiac myocytes derived from human induced pluripotent stem cells (hiPSC-CMs) show heterogeneous action potentials (APs), probably due to different expression patterns of membrane ionic currents. We developed a method for determining expression patterns of functional channels in terms of whole-cell ionic conductance (Gx) using individual spontaneous AP configurations. It has been suggested that apparently identical AP configurations can be obtained using different sets of ionic currents in mathematical models of cardiac membrane excitation. If so, the inverse problem of Gx estimation might not be solved. We computationally tested the feasibility of the gradient-based optimization method. For a realistic examination, conventional 'cell-specific models' were prepared by superimposing the model output of AP on each experimental AP recorded by conventional manual adjustment of Gxs of the baseline model. Gxs of 4-6 major ionic currents of the 'cell-specific models' were randomized within a range of ± 5-15% and used as an initial parameter set for the gradient-based automatic Gxs recovery by decreasing the mean square error (MSE) between the target and model output. Plotting all data points of the MSE-Gx relationship during optimization revealed progressive convergence of the randomized population of Gxs to the original value of the cell-specific model with decreasing MSE. The absence of any other local minimum in the global search space was confirmed by mapping the MSE by randomizing Gxs over a range of 0.1-10 times the control. No additional local minimum MSE was obvious in the whole parameter space, in addition to the global minimum of MSE at the default model parameter.


Assuntos
Células-Tronco Pluripotentes Induzidas , Humanos , Potenciais de Ação/fisiologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Transporte de Íons , Miócitos Cardíacos/metabolismo
6.
Int J Mol Sci ; 23(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36361659

RESUMO

Lens ion homeostasis depends on Na,K-ATPase and NKCC1. TRPV4 and TRPV1 channels, which are mechanosensitive, play important roles in mechanisms that regulate the activity of these transporters. Here, we examined another mechanosensitive channel, piezo1, which is also expressed in the lens. The purpose of the study was to examine piezo1 function. Recognizing that activation of TRPV4 and TRPV1 causes changes in lens ion transport mechanisms, we carried out studies to determine whether piezo1 activation changes either Na,K-ATPase-mediated or NKCC1-mediated ion transport. We also examined channel function of piezo1 by measuring calcium entry. Rb uptake was measured as an index of inwardly directed potassium transport by intact mouse lenses. Intracellular calcium concentration was measured in Fura-2 loaded cells by a ratiometric imaging technique. Piezo1 immunolocalization was most evident in the lens epithelium. Potassium (Rb) uptake was increased in intact lenses as well as in cultured lens epithelium exposed to Yoda1, a piezo1 agonist. The majority of Rb uptake is Na,K-ATPase-dependent, although there also is a significant NKCC-dependent component. In the presence of ouabain, an Na,K-ATPase inhibitor, Yoda1 did not increase Rb uptake. In contrast, Yoda1 increased Rb uptake to a similar degree in the presence or absence of 1 µM bumetanide, an NKCC inhibitor. The Rb uptake response to Yoda1 was inhibited by the selective piezo1 antagonist GsMTx4, and also by the nonselective antagonists ruthenium red and gadolinium. In parallel studies, Yoda1 was observed to increase cytoplasmic calcium concentration in cells loaded with Fura-2. The calcium response to Yoda1 was abolished by gadolinium or ruthenium red. The calcium and Rb uptake responses to Yoda1 were absent in calcium-free bathing solution, consistent with calcium entry when piezo1 is activated. Taken together, these findings point to stimulation of Na,K-ATPase, but not NKCC, when piezo1 is activated. Na,K-ATPase is the principal mechanism responsible for ion and water homeostasis in the lens. The functional role of lens piezo1 is a topic for further study.


Assuntos
ATPase Trocadora de Sódio-Potássio , Canais de Cátion TRPV , Camundongos , Animais , Canais de Cátion TRPV/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Rutênio Vermelho , Gadolínio , Fura-2 , Potássio/metabolismo , Sódio/metabolismo , Transporte de Íons , Canais Iônicos/metabolismo
7.
Chempluschem ; 87(11): e202200266, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36414387

RESUMO

The development of synthetic anion transporters is motivated by their potential application as treatment for diseases that originate from deficient anion transport by natural proteins. Transport of bicarbonate is important for crucial biological functions such as respiration and digestion. Despite this biological relevance, bicarbonate transport has not been as widely studied as chloride transport. Herein we present an overview of the synthetic receptors that have been studied as bicarbonate transporters, together with the different assays used to perform transport studies in large unilamellar vesicles. We highlight the most active transporters and comment on the nature of the functional groups present in active and inactive compounds. We also address recent mechanistic studies that have revealed different processes that can lead to net transport of bicarbonate, as well as studies reported in cells and tissues, and comment on the key challenges for the further development of bicarbonate transporters.


Assuntos
Bicarbonatos , Transporte Biológico , Transporte de Íons
8.
Proc Natl Acad Sci U S A ; 119(48): e2214602119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36409899

RESUMO

The function of many channels and transporters is enriched by the conformational plasticity of intrinsically disordered regions (IDRs). Copper transporter 1 (Ctr1) is the main entry point for Cu(I) ions in eukaryotes and contains IDRs both at its N-terminal (Nterm) and C-terminal ends. The former delivers copper ions from the extracellular matrix to the selectivity filter in the Ctr1 lumen. However, the molecular mechanism of this process remains elusive due to Nterm's disordered nature. Here, we combine advanced molecular dynamics simulations and circular dichroism experiments to show that Cu(I) ions and a lipidic environment drive the insertion of the Nterm into the Ctr1 selectivity filter, causing its opening. Through a lipid-aided conformational switch of one of the transmembrane helices, the conformational change of the selectivity filter propagates down to the cytosolic gate of Ctr1. Taken together, our results elucidate how conformational variability of IDRs modulates ion transport.


Assuntos
Cobre , Simulação de Dinâmica Molecular , Íons , Transporte de Íons
9.
Phys Chem Chem Phys ; 24(44): 27157-27162, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36345725

RESUMO

Two-dimensional MXenes have become a crucial topic in the field of ion transportation owing to their excellent electrochemical performance. Herein, a strategy for preparing a layered MXene-graphene oxide (GO) membrane via vacuum filtration is proposed, which endows the delaminated two-dimensional MXene-GO membrane (MGOm) with excellent electrical conductivity and chemical stability, achieving an excellent voltage-gated ion transport behavior. Owing to the presence of charges or dipoles within the membrane's channel, the movement of electrons or dipoles under the influence of membrane potential is possible. By varying the transmembrane potential, the transition between the closed and open states of the voltage-gated ion channel can be adjusted. When a negative potential is applied at osmotic pressure, the force between the charged MGOm sheet and the cation (K+) is enhanced, promoting ion permeation. Conversely, the application of positive potential attenuates electrostatic attraction, resulting in a decrease in ion permeability. In addition, the effects of MXene and GO with different modulation ratios on the voltage-gated ion transport have shown that when the modulation ratio of MXene : GO is 7 : 3, the optimal ion permeation rate is achieved. In conclusion, the conductive film with voltage-gated nanochannels is a promising alternative for ion transportation, opening up new avenues for the further exploration of MXene materials in energy storage devices.


Assuntos
Grafite , Transporte de Íons , Membranas , Condutividade Elétrica
10.
PLoS One ; 17(11): e0277096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36399482

RESUMO

Vasoactive intestinal peptide (VIP) as a neurocrine factor released by enteric neurons has been postulated to participate in the regulation of transcellular active calcium transport across intestinal epithelium, but the preceding evidence is scant and inconclusive. Herein, transepithelial calcium flux and epithelial electrical parameters were determined by Ussing chamber technique with radioactive tracer in the intestinal epithelium-like Caco-2 monolayer grown on Snapwell. After 3-day culture, Caco-2 cells expressed mRNA of calcium transporters, i.e., TRPV6, calbindin-D9k, PMCA1b and NCX1, and exhibited transepithelial resistance of ~200 Ω cm2, a characteristic of leaky epithelium similar to the small intestine. VIP receptor agonist was able to enhance transcellular calcium flux, whereas VIP receptor antagonist totally abolished calcium fluxes induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Since the intestinal cystic fibrosis transmembrane conductance regulator (CFTR) could be activated by VIP and calciotropic hormones, particularly parathyroid hormone, we sought to determine whether CFTR also contributed to the 1,25(OH)2D3-induced calcium transport. A selective CFTR inhibitor (20-200 µM CFTRinh-172) appeared to diminish calcium fluxes as well as transepithelial potential difference and short-circuit current, both of which indicated a decrease in electrogenic ion transport. On the other hand, 50 µM genistein-a molecule that could rapidly activate CFTR-was found to increase calcium transport. Our in silico molecular docking analysis confirmed direct binding of CFTRinh-172 and genistein to CFTR channels. In conclusion, VIP and CFTR apparently contributed to the intestinal calcium transport, especially in the presence of 1,25(OH)2D3, thereby supporting the existence of the neurocrine control of intestinal calcium absorption.


Assuntos
Cálcio , Regulador de Condutância Transmembrana em Fibrose Cística , Humanos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Cálcio/metabolismo , Peptídeo Intestinal Vasoativo/farmacologia , Peptídeo Intestinal Vasoativo/metabolismo , Células CACO-2 , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Genisteína/metabolismo , Simulação de Acoplamento Molecular , Transporte de Íons , Mucosa Intestinal/metabolismo , Cálcio na Dieta/metabolismo
11.
Nat Commun ; 13(1): 6669, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335134

RESUMO

Biological ion channels rely on ions as charge carriers and unidirectional ion flow to produce and transmit signals. To realize artificial biological inspired circuitry and seamless human-machine communication, ion-transport-based rectification devices should be developed. In this research, poly(methyl methacrylate) (PMMA) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) gel polymer electrolytes (GPEs) are assembled to construct a novel ionic diode, enabling ion rectification through ion-diffusion/migration that emulates biological systems. This ion rectification results from the different diffusion/migration behaviors of mobile ions transporting in the GPE heterojunction. The electrical tests of the GPE heterojunction reveal outstanding rectifying ratio of 23.11. The GPE ionic diode operates in wide temperature window, from -20 °C (anti-freezing) to 125 °C (thermal tolerance). The absence of redox reactions is verified in the cyclic voltammogram. The GPE ionic diodes are used to construct ionic logic gates for signal communication. Furthermore, rectification of a triboelectric nanogenerator and potential for synaptic devices are demonstrated.


Assuntos
Eletrólitos , Polímeros , Humanos , Íons , Polimetil Metacrilato , Transporte de Íons
12.
Fluids Barriers CNS ; 19(1): 92, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36419095

RESUMO

BACKGROUND: Folates are a family of B9 vitamins that serve as one-carbon donors critical to biosynthetic processes required for the development and function of the central nervous system (CNS) in mammals. Folate transport is mediated by three highly specific systems: (1) folate receptor alpha (FRα; FOLR1/Folr1), (2) the reduced folate-carrier (RFC; SLC19A1/Slc19a1) and (3) the proton-coupled folate transporter (PCFT; SLC46A1/Slc46a1). Folate transport into and out of the CNS occurs at the blood-cerebrospinal fluid barrier (BCSFB), mediated by FRα and PCFT. Impairment of folate transport at the BCSFB results in cerebral folate deficiency in infants characterized by severe neurological deficiencies and seizures. In contrast to the BCSFB, CNS folate transport at other brain barriers and brain parenchymal cells has not been extensively investigated. The aim of this study is to characterize folate transport systems in the murine CNS at several known barriers encompassing the BCSFB, arachnoid barrier (AB), blood-brain barrier (BBB) and parenchymal cells (astrocytes, microglia, neurons). METHODS: Applying immunohistochemistry, localization of folate transport systems (RFC, PCFT, FRα) was examined at CNS barriers and parenchymal sites in wildtype (C57BL6/N) mice. Subcellular localization of the folate transport systems was further assessed in an in vitro model of the mouse AB. Gene and protein expression was analyzed in several in vitro models of brain barriers and parenchyma by qPCR and western blot analysis. RESULTS: RFC, PCFT, and FRα expression was localized within the BCSFB and BBB consistent with previous reports. Only RFC and PCFT expression was detected at the AB. Varied levels of RFC and PCFT expression were detected in neuronal and glial cells. CONCLUSIONS: Localization of RFC and PCFT within the AB, described here for the first time, suggest that AB may contribute to folate transport between the peripheral circulation and the CSF. RFC and PCFT expression observed in astrocytes and microglia is consistent with the role that one or both of these transporters may play in delivering folates into cells within brain parenchyma. These studies provide insights into mechanisms of folate transport in the CNS and may enhance our understanding of the critical role folates play in neurodevelopment and in the development of novel treatment strategies for disorders of brain folate deficiency due to impaired transporter function.


Assuntos
Encéfalo , Sistema Nervoso Central , Animais , Camundongos , Transporte de Íons , Barreira Hematoencefálica , Ácido Fólico , Mamíferos , Transportador de Folato Acoplado a Próton
13.
J Phys Chem B ; 126(44): 8985-8999, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36306164

RESUMO

Computer simulations are reported on Ac-LS3, a synthetic ion channel, containing 21 residues with a Leu-Ser-Ser-Leu-Leu-Ser-Leu heptad repeat, which forms ions channels upon application of voltage. A hexameric, coiled-coil bundle initially positioned perpendicular to the membrane settled into a stable, tilted structure after 1.5 µs, most likely to improve contacts between the non-polar exterior of the channel and the hydrophobic core of the membrane. Once tilted, the bundle remained in this state during subsequent simulations of nearly 10 µs at voltages ranging from 200 to -100 mV. In contrast, attempts to identify a stable pentameric structure failed, thus supporting the hypothesis that the channel is a hexamer. Results at 100 mV were used to reconstruct the free energy profiles for K+ and Cl- in the channel. This was done by way of several methods in which results of molecular dynamics (MD) simulations were combined with the electrodiffusion model. Two of them developed recently do not require knowledge of the diffusivity. Instead, they utilize one-sided density profiles and committor probabilities. The consistency between different methods is very good, supporting the utility of the newly developed methods for reconstructing free energies of ions in channels. The flux of K+, which accounts for most of the current through the channel, calculated directly from MD matches well the total measured current. However, the current of Cl- is somewhat overestimated, possibly due to a slightly unbalanced force field involving chloride. The current-voltage dependence was also reconstructed by way of a recently developed, efficient method that requires simulations only at a single voltage, yielding good agreement with the experiment. Taken together, the results demonstrate that computational electrophysiology has become a reliable tool for studying how channels mediate ion transport through membranes.


Assuntos
Canais Iônicos , Simulação de Dinâmica Molecular , Canais Iônicos/química , Transporte de Íons , Cloretos/metabolismo
14.
Org Biomol Chem ; 20(40): 7981-7986, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36196986

RESUMO

A new family of squaramide-based anionophores (L1-L8) have been synthesised and fully characterised with the aim to investigate the effect of indolyl substituents on their anion binding and transmembrane transport properties. L1, L2, L6, and L8, bearing a 7-indolyl/indol-7-yl moiety as the substituent, were found to be the most efficient of the series in binding chloride with high stability constants. L1, L6, and L8 were also found to be the most potent anionophores of the series, able to mediate transmembrane anion transport. In particular, L6 bearing the 3,5-bis(trifluoromethyl)phenyl group was found to be the most active transporter, and its efficiency as an anionophore/anion transporter was favourably compared with that of their symmetrically-substituted squaramide analogues L9 and L10, previously reported in the literature.


Assuntos
Cloretos , Quinina , Cloretos/metabolismo , Transporte de Íons , Ânions/química
15.
Biosens Bioelectron ; 218: 114741, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36209531

RESUMO

Light-driven proton directional transport is important in living beings as it could subtly realize the light energy conversion for living uses. In the past years, 2D materials-based nanochannels have shown great potential in active ion transport due to controllable properties, including surface charge distribution, wettability, functionalization, electric structure, and external stimuli responsibility, etc. However, to fuse the inorganic materials into bio-membranes still faces several challenges. Here, we proposed peptide-modified WS2 nanosheets via cysteine linkers to realize tunable band structure and, hence, enable light-driven proton transmembrane transport. The modification was achieved through the thiol chemistry of the -SH groups in the cysteine linker and the S vacancy on the WS2 nanosheets. By tuning the amino residues sequences (lysine-rich peptides, denoted as KFC; and aspartate-rich peptides, denoted as DFC), the ζ-potential, surface charge, and band energy of WS2 nanosheets could be rationally regulated. Janus membranes formed by assembling the peptide-modified WS2 nanosheets could realize the proton transmembrane transport under visible light irradiation, driven by a built-in potential due to a type II band alignment between the KFC-WS2 and DFC-WS2. As a result, the proton would be driven across the formed nanochannels. These results demonstrate a general strategy to build bio-semiconductor materials and provide a new way for embedding inorganic materials into biological systems toward the development of bioelectronic devices.


Assuntos
Técnicas Biossensoriais , Prótons , Cisteína , Ácido Aspártico , Lisina , Transporte de Íons , Semicondutores , Peptídeos
16.
Small Methods ; 6(11): e2200761, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36196624

RESUMO

Ionic signal amplification is a key challenge for single-molecule analyses by solid-state nanopore sensing. Here, a permittivity gradient approach for amplifying ionic blockade characteristics of DNA in a nanofluidic channel is reported. The transmembrane ionic current response is found to change substantially through modifying the liquid permittivity at one side of a pore with an organic solvent. Imposing positive liquid permittivity gradients with respect to the direction of DNA electrophoresis, this study observes the resistive ionic signals to become larger due to the varying contributions of molecular counterions. On the contrary, negative gradients render adverse effects causing conductive ionic current pulses upon polynucleotide translocations. Most importantly, both the positive and negative gradients are demonstrated to be capable of amplifying the ionic signals by an order of magnitude with a 1.3-fold difference in the transmembrane liquid dielectric constants. This phenomenon allows a novel way to enhance the single-molecule sensitivity of nanopore sensing that may be useful in analyzing secondary structures and genome sequence of DNA by ionic current measurements.


Assuntos
Nanoporos , DNA/análise , Íons , Nanotecnologia , Transporte de Íons
17.
ACS Nano ; 16(10): 17128-17138, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36222833

RESUMO

Accurate measurements of ion permeability through cellular membranes remains challenging due to the lack of suitable ion-selective probes. Here we use giant unilamellar vesicles (GUVs) as membrane models for the direct visualization of mass translocation at the single-vesicle level. Ion transport is indicated with a fluorescently adjustable DNA-based sensor that accurately detects sub-millimolar variations in K+ concentration. In combination with microfluidics, we employed our DNA-based K+ sensor for extraction of the permeation coefficient of potassium ions. We measured K+ permeability coefficients at least 1 order of magnitude larger than previously reported values from bulk experiments and show that permeation rates across the lipid bilayer increase in the presence of octanol. In addition, an analysis of the K+ flux in different concentration gradients allows us to estimate the complementary H+ flux that dissipates the charge imbalance across the GUV membrane. Subsequently, we show that our sensor can quantify the K+ transport across prototypical cation-selective ion channels, gramicidin A and OmpF, revealing their relative H+/K+ selectivity. Our results show that gramicidin A is much more selective to protons than OmpF with a H+/K+ permeability ratio of ∼104.


Assuntos
Gramicidina , Lipossomas Unilamelares , Bicamadas Lipídicas , Prótons , Transporte de Íons , Canais Iônicos , Íons , Potássio , DNA , Octanóis
18.
Biomolecules ; 12(10)2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36291682

RESUMO

One of the most common biochemical processes is the proton transfer through the cell membranes, having significant physiological functions in living organisms. The proton translocation mechanism has been extensively studied; however, mechanistic details of this transport are still needed. During the last decades, the field of artificial proton channels has been in continuous growth, and understanding the phenomena of how confined water and channel components mediate proton dynamics is very important. Thus, proton transfer continues to be an active area of experimental and theoretical investigations, and acquiring insights into the proton transfer mechanism is important as this enlightenment will provide direct applications in several fields. In this review, we present an overview of the development of various artificial proton channels, focusing mostly on their design, self-assembly behavior, proton transport activity performed on bilayer membranes, and comparison with protein proton channels. In the end, we discuss their potential applications as well as future development and perspectives.


Assuntos
Biomimética , Prótons , Canais Iônicos/química , Transporte de Íons , Água/química
19.
Phys Chem Chem Phys ; 24(40): 24866-24872, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36196854

RESUMO

Ability to control ionic current flowing through a nanopore has been demonstrated using the electric field effect on an electrical gate surrounding the nanopore. The gate electrode was introduced onto a single nanopore by depositing an Au layer on a silicon nitride diaphragm prior to pore milling using a focused ion beam technique. A hafnium oxide layer was subsequently deposited onto the nanopore structure as an insulating layer to protect the gate electrode. The device operation was investigated in KCl electrolyte and the ionic current regulating ability was examined under the influence of the gate voltage and the nanopore size. It was found that the device shows significant ionic current response with respect to the applied gate voltage. The resulting electric field dependent behavior of the fabricated nanopore suggests that the ionic current is influenced by positive surface charge inside the nanopore. The gate influence was more pronounced in the smaller nanopore and with higher source-drain voltage. The gate and pore size dependence behavior allows the potential to regulate ionic current as a nanoscale valve in nanochannel applications.


Assuntos
Nanoporos , Transporte de Íons , Eletrodos , Eletricidade , Eletrólitos
20.
Langmuir ; 38(41): 12450-12456, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36197723

RESUMO

Recently, bioinspired 2D material-based nanofluidic systems with unique properties and advantages have been receiving considerable research interest and getting rapid development. However, it remains a huge challenge to integrate adaptive responsiveness to external stimuli and asymmetric ion transport characteristics into the 2D nanofluidic systems. Herein, we report a dual-driven switchable asymmetric ionic transport phenomenon through a graphene oxide-based heterogeneous 2D nanofluidic membrane. Taking advantage of the formation of a charge heterojunction induced by the variation of pH or UV irradiation, a maximum ionic current rectification (ICR) ratio of ca. 56 for pH or 140 for light was achieved. Such smart nanofluidic devices with pH and light dual-responsiveness and asymmetric ion transport behaviors provide a universal strategy for potential applications in chemical sensing, water treatment, and energy conversion and establish a promising platform for exploring advanced quantum ionics biodevices with ultrafast signal transmission, nanochannel-structured bioreactors with high efficiency, etc.


Assuntos
Materiais Biomiméticos , Nanoestruturas , Materiais Biomiméticos/química , Transporte de Íons , Íons/química , Nanoestruturas/química
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