Single-ion-conducted covalent organic framework serving as Li-ion pump in polyethylene oxide-based electrolyte for robust solid-state Li-S batteries.

Poly(ethylene oxide) (PEO)-based electrolytes are widely used for building solid-state lithium-sulfur (Li-S) batteries but suffer from poor lithium-ion (Li+) transportation kinetics. Here, a lithium-sulfonated covalent organic framework (TpPa-SO3Li) was synthesized and functionalized as a Li+ pump in a PEO-based solid-state electrolyte to fabricate robust Li-S batteries. The designed TpPa-SO3, Li with its porous skeleton and abundant lithium sulfonate groups not only provided iontransport channels but also enhanced the fast migration of Li+. The PEO composite electrolyte containing 5 %-TpPa-SO3Li exhibited a notable ionic conductivity of 6.28 × 10-4 S cm-1 and an impressive Li+ transference number of 0.78 at 60 °C. As a result, Li-Li symmetric batteries with the optimized PEO/TpPa-SO3Li composite electrolyte stably cycled for 300 h, with a minimal overpotential of only 100 mV at 0.5 mA cm-2. Moreover, the customized solid-state Li-S batteries based on PEO/TpPa-SO3Li were stable for 600 cycles at 60 oC with a high Coulombic efficiency of approximately 98 %. This study provides a promising strategy for introducing covalent-organic-framework (COF)-based Li+ pumps to build robust solid-state Li-S batteries.

Direct detection of the chloride release and uptake reactions of Natronomonas pharaonis halorhodopsin.

Membrane transport proteins undergo multistep conformational changes to fulfill the transport of substrates across biological membranes. Substrate release and uptake are the most important events of these multistep reactions that accompany significant conformational changes. Thus, their relevant structural intermediates should be identified to better understand the molecular mechanism. However, their identifications have not been achieved for most transporters due to the difficulty of detecting the intermediates. Herein, we report the success of these identifications for a light-driven chloride transporter halorhodopsin (HR). We compared the time course of two flash-induced signals during a single transport cycle. One is a potential change of Cl--selective membrane, which enabled us to detect tiny Cl--concentration changes due to the Cl- release and the subsequent Cl--uptake reactions by HR. The other is the absorbance change of HR reflecting the sequential formations and decays of structural intermediates. Their comparison revealed not only the intermediates associated with the key reactions but also the presences of two additional Cl--binding sites on the Cl--transport pathways. The subsequent mutation studies identified one of the sites locating the protein surface on the releasing side. Thus, this determination also clarified the Cl--transport pathway from the initial binding site until the release to the medium.

Wood Ion Pumps Enabled by Light-Responsive MoS2-Decorated Nanocellulosic Channels.

Light-driven active ion transport discovered in nanomaterials (e.g., graphene, metal-organic framework, and MXene) implicates crucial applications in membrane-based technology and energy conversion systems. However, it remains a challenge to achieve bulk assembly. Herein, we employ the scalable wood as a framework for in situ growth of MoS2 nanosheets to facilitate light-responsive ion transport. Owing to the aligned and negatively charged wood nanochannels, the MoS2-decorated wood exhibits an excellent nanofluidic conductivity of 8.3 × 10-5 S cm-1 in 1 × 10-6 M KCl. Asymmetric light illumination creates the separation of electrons and holes in MoS2 nanosheets, enabling ions to move uphill against a wide range of concentration gradients. As a result, the MoS2-decorated wood can pump ions uphill against a 20-fold concentration gradient at a light intensity of 300 mW cm-2. When the illumination is applied to the opposite side, the osmotic current along the 20-fold concentration gradient can be enhanced to 75.1 nA, and the corresponding osmotic energy conversion power density increases to more than 12.6 times that of the nonilluminated state. Based on the light-responsive behaviors, we are extending the use of MoS2-decorated wood as the ionic elements for nanofluidic circuits, such as ion switches, ion diodes, and ion transistors. This work provides a facile and scalable strategy for fabricating light-controlled nanofluidic devices from biomass materials.

Light-Powered Directional Ion Transport via PFN-Br/MoS2 Heterogeneous Membranes: Band Alignment and Activation Energy Barrier Engineering.

Biological photoresponsive ion transport systems consistently attract researchers' attention owing to their remarkable functions of harvesting energy from nature and participating in visual perception systems. Designing and constructing artificial light-driven ion transport devices to mimic biological counterparts remains a challenge owing to fabrication limitations in nanoconfined spaces. Herein, a typical conjugated polyelectrolyte (PFN-Br) was assembled onto a laminated MoS2M using simple solution-processing vacuum filtration, resulting in a heterogeneous three- and two-dimensional nanoporous membrane. The designed band alignment between PFN-Br and MoS2 enables effective directional ion transport under irradiation in an equilibrium solution, even against a 30-fold concentration gradient. The staggered energy structure of PFN-Br and MoS2 enhances charge separation and establishes a photogenerated potential as the driving force for ion transport. Additionally, the activation energy barrier for ion transport across the heterogeneous membrane decreased by 60% after light irradiation, considerably improving ion transport flux. The easy fabrication and high performance of the membrane in light-powered ion transport provide promising approaches for designing nanofluidic devices with possible applications in energy conversion, light-enhanced biosensing, and photoresponsive ionic devices.

Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype.

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels. The roles of ion channels in cancer are consistent with the importance of bioelectrical parameters in cell regulation and with the functions of bioelectric signaling in morphogenetic signals that act as cancer suppressors. We find that compounds that are well-known for having targets in the nervous system, such as voltage-gated ion channels, ligand-gated ion channels, proton pumps, and gap junctions are especially relevant to cancer. Our review suggests further opportunities for the repurposing of numerous promising candidates in the field of cancer electroceuticals.

Na+/K+-ATPase: More than an Electrogenic Pump.

The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA's role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell-cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA ß-subunits as cell adhesion molecules in glia and epithelial cells.

Morphology-Controlled Ion Transport in Mixed-Orientation Polymers.

Advancing iontronics with precisely controlled ion transport is fundamentally important to bridge external organic electronics with the biosystem. This long-standing goal, however, is thus far limited by the trade-off between the active ion electromigration and idle diffusion leakage in the (semi)crystalline film. Here, we presented a mixed-orientation strategy by blending a conjugated polymer, allowing for simultaneously high ion electromigration efficiency and low leakage. Our studies revealed that edge-on aggregation with a significant percolative pathway exhibits much higher ion permeability than that of the face-on counterpart but encounters pronounced leakage diffusion. Through carefully engineering the mixed orientations, the polymer composite demonstrated an ideal switchable ion-transport behavior, achieving a remarkably high electromigration efficiency exceeding one quadrillion ions per milliliter per minute and negligible idle leakage. This proof of concept, validated by drug release in a skin-conformable organic electronic ion pump (OEIP), offers a rational approach for the development of multifunctional iontronic devices.

Ultra-High Vacuum Cells Realized by Miniature Ion Pump Using High-Efficiency Plasma Source.

In recent years, there has been significant interest in quantum technology, characterized by the emergence of quantum computers boasting immense processing power, ultra-sensitive quantum sensors, and ultra-precise atomic clocks. Miniaturization of quantum devices using cold atoms necessitates the employment of an ultra-high vacuum miniature cell with a pressure of approximately 10-6 Pa or even lower. In this study, we developed an ultra-high vacuum cell realized by a miniature ion pump using a high-efficiency plasma source. Initially, an unsealed miniature ion pump was introduced into a vacuum chamber, after which the ion pump's discharge current, depending on vacuum pressures, was evaluated. Subsequently, a miniature vacuum cell was fabricated by hermetically sealing the miniature vacuum pump. The cell was successfully evacuated by a miniature ion pump down to an ultra-high vacuum region, which was derived by the measured discharge current. Our findings demonstrate the feasibility of achieving an ultra-high vacuum cell necessary for the operation of miniature quantum devices.

Photo-Driven Ion Directional Transport across Artificial Ion Channels: Band Engineering of WS2 via Peptide Modification.

Biological photo-responsive ion channels play important roles in the important metabolic processes of living beings. To mimic the unique functions of biological prototypes, the transition metal dichalcogenides, owing to their excellent mechanical, electrical, and optical properties, are already used for artificial intelligent channel constructions. However, there remain challenges to building artificial bio-semiconductor nanochannels with finely tuned band gaps for accurately simulating or regulating ion transport. Here, two well-designed peptides are employed for the WS2 nanosheets functionalization with the sequences of PFPFPFPFC and DFDFDFDFC (PFC and DFC; P: proline, D: aspartate, and F: phenylalanine) through cysteine (Cys, C) linker, and an asymmetric peptide-WS2 membrane (AP-WS2M) could be obtained via self-assembly of peptide-WS2 nanosheets. The AP-WS2M could realize the photo-driven anti-gradient ion transport and vis-light enhanced osmotic energy conversion by well-designed working patterns. The photo-driven ion transport mechanism stems from a built-in photovoltaic motive force with the help of formed type II band alignment between the PFC-WS2 and DFC-WS2. As a result, the ions would be driven across the channels of the membrane for different applications. The proposed system provides an effective solution for building photo-driven biomimetic 2D bio-semiconductor ion channels, which could be extensively applied in the fields of drug delivery, desalination, and energy conversion.

Photosynthetic-Membrane-Like Ion Translocation in Visible-Light-Harvesting Nanofluidic Channels.

The selective uphill and downhill movement of protons in and out of photosynthetic membrane enabled by ion pumps and ion channels is key to photosynthesis. Reproducing the functions of photosynthetic membranes in artificial systems has been a persistent goal. Here, a visible-light-harvesting nanofluidic channels is reported which experimentally demonstrates the ion translocation functions of photosynthetic membranes. A molecular junction consisting of photosensitive ruthenium complexes linked to TiO2 electron acceptors forms the reaction centers in the nanofluidic channels. The visible-light-triggered vectorial electron injection into TiO2 establishes a difference in transmembrane potential across the channels, which enables uphill transport of ions against a 5-fold concentration gradient. In addition, the asymmetric charge distribution across the channels enables the unidirectional downhill movement of ions, demonstrating an ion rectification effect with a ratio of 18:1. This work, for the first time, mimics both the uphill and downhill ion translocation functions of photosynthetic membranes, which lays a foundation for nanofluidic energy conversion.

Bio-inspired High-Performance Artificial Ion Pump Mediated by Subnanoscale Dehydration Hydration Effects.

The energy conversion in plant chloroplast is carried out by pumping protons into the thylakoid for driving ATP synthesis. Inspired by ion active transport in living organisms, we attempted to design an artificial ion pump induced by subnanoconfinement effects. This ionic device uses two polarity functional nanoporous films as ion-selective valves at both ends and UiO-66 metal-organic framework-filled microchannels as ion storage cavities. In the charging process, ions could be pumped into the central cavities by nanovalves, which produced an ion gradient 10 to 100 times higher than the bulk, and were trapped within the subnanocages by dehydration. In the discharging process, the enriched ions were rehydrated and slowly released by the surface charge of the nanovalves, producing a sustainable ion current. The ion storage efficiency of this nanofluidic device could be improved to 60.3%, and the release time of ion current was also prolonged by 1 order of magnitude. This work combines the active and passive transport of ions to realize fast storage and slow release of ionic current, which provides an ion gradient-mediated novel energy conversion strategy.

Retinal-Based Anion Pump from the Cyanobacterium Tolypothrix campylonemoides.

In this work, TcaR rhodopsin from the cyanobacterium Tolypothrix campylonemoides was characterized. Analysis of the amino acid sequence of TcaR revealed that this protein possesses a TSD motif that differs by only one amino acid from the TSA motif of the known halorhodopsin chloride pump. The TcaR protein was expressed in E. coli, purified, and incorporated into proteoliposomes and nanodiscs. Functional activity was measured by electric current generation through the planar bilayer lipid membranes (BLMs) with proteoliposomes adsorbed on one side of the membrane surface, as well as by fluorescence using the voltage-dependent dye oxonol VI. We have shown that TcaR rhodopsin functions as a powerful anion pump. Our results show that the novel microbial anion transporter, TcaR, deserves deeper investigation and may be of interest both for fundamental studies of membrane proteins and as a tool for optogenetics.

Multistep conformational changes leading to the gate opening of light-driven sodium pump rhodopsin.

Membrane transport proteins require a gating mechanism that opens and closes the substrate transport pathway to carry out unidirectional transport. The "gating" involves large conformational changes and is achieved via multistep reactions. However, these elementary steps have not been clarified for most transporters due to the difficulty of detecting the individual steps. Here, we propose these steps for the gate opening of the bacterial Na+ pump rhodopsin, which outwardly pumps Na+ upon illumination. We herein solved an asymmetric dimer structure of Na+ pump rhodopsin from the bacterium Indibacter alkaliphilus. In one protomer, the Arg108 sidechain is oriented toward the protein center and appears to block a Na+ release pathway to the extracellular (EC) medium. In the other protomer, however, this sidechain swings to the EC side and then opens the release pathway. Assuming that the latter protomer mimics the Na+-releasing intermediate, we examined the mechanism for the swing motion of the Arg108 sidechain. On the EC surface of the first protomer, there is a characteristic cluster consisting of Glu10, Glu159, and Arg242 residues connecting three helices. In contrast, this cluster is disrupted in the second protomer. Our experimental results suggested that this disruption is a key process. The cluster disruption induces the outward movement of the Glu159-Arg242 pair and simultaneously rotates the seventh transmembrane helix. This rotation resultantly opens a space for the swing motion of the Arg108 sidechain. Thus, cluster disruption might occur during the photoreaction and then trigger sequential conformation changes leading to the gate-open state.

The FSH-mTOR-CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins.

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

Protonation of Asp116 and distortion of the all-trans retinal chromophore in Krokinobacter eikastus rhodopsin 2 causes a redshift in absorption maximum upon dehydration.

Water is usually indispensable for protein function. For ion-pumping rhodopsins, water molecules inside the proteins play an important role in ion transportation. In addition to amino acid residues, water molecules regulate the colors of retinal proteins. It was reported that a sodium-pumping rhodopsin, Krokinobacter eikastus rhodopsin 2 (KR2), showed a color change from red to purple upon dehydration under crystalline conditions. Here, we applied comprehensive visible and IR absorption spectroscopy and resonance Raman spectroscopy to KR2 in liposomes under hydration-controlled conditions. A large increase in the hydrogen-out-of-plane (HOOP) vibration at 947 (H-C11=C12-H Au mode) and moderate increases at 893 (C7-H and C10-H) and 808 (C14-H) cm-1 were observed under dehydrated conditions, which were assigned by using systematically deuterated retinal. Moreover, the Asn variant at Asp116, which functions as a counter ion for the protonated retinal Schiff base (PRSB), caused a large redshift in the absorption maximum and constitutive increase in the HOOP modes under hydrated and dehydrated conditions. The protonation of a counter ion at Asp116 clearly causes a redshift in the absorption maximum as the all-trans retinal chromophore twists upon dehydration. Namely, the results strongly suggested that water molecules are important for maintaining the hydrogen-bonding network at the PRSB and deprotonation state of Asp116 in KR2.

Concerted primary proton transfer reactions in a thermophilic rhodopsin studied by time-resolved infrared spectroscopy at high temperature.

The primary proton transfer reactions of thermophilic rhodopsin, which was first discovered in an extreme thermophile, Thermus thermophilus JL-18, were investigated using time-resolved Fourier transform infrared spectroscopy at various temperatures ranging from 298 to 343 K (25 to 70 °C) and proton transport activity analysis. The analyses were performed using counterion (D95E, D95N, D229E, and D229N) and proton donor mutants (E106D and E106Q) as well. First, the initial proton transfer from the protonated retinal Schiff base (PRSB) to D95 was identified. The temperature dependency showed that the proton transfer reaction in the intermediate states dramatically changed above 318 K (45 °C). In addition, the proton transfer reaction correlated well with the structural change from turn to ß-strand in the protein moiety, suggesting that this step may be regulated by the rigidity of the loop region. We also elucidated that the proton transfer reaction from proton donor E106 to the retinal Schiff base occurred synchronously with the primary proton transfer from the PRSB to D95. Surprisingly, we discovered that the direction of proton transfer was regulated by the secondary counterion, D229. Comparative analysis of Gloeobacter rhodopsin from the mesophile, Gloeobacter violaceus, highlighted that the primary proton transfer reactions in thermophilic rhodopsin were optimized at high temperatures partly due to the specific turn to ß-strand structural change. This was not observed in Gloeobacter rhodopsin and other related proteins such as bacteriorhodopsin.

Genome wide identification and characterization of MATE family genes in mangrove plants.

Multidrug and Toxic Compound Extrusion (MATE) proteins are essential transporters that extrude metabolites and participate in plant development and cellular detoxification. MATE transporters, which play crucial roles in the survival of mangrove plants under highly challenged environments, by specialized salt extrusion mechanisms, are mined from their genomes and reported here for the first time. Through homology search and domain prediction in the genome assemblies of Avicennia marina, Bruguiera sexangula, Ceriops zippeliana, Kandelia obovata, Rhizophora apiculata and Ceriops tagal, 74, 68, 66, 66, 63 and 64 MATE proteins, respectively were identified. The phylogenetic analysis divided the identified proteins into five major clusters and following the clustering pattern of the functionally characterized proteins, functions of the transporters in each cluster were predicted. Amino acid sequences, exon-intron structure, motif details and subcellular localization pattern for all the 401 proteins are described. The custom designed repeat masking libraries generated for each of these genomes, which will be of extensive use for the researchers worldwide, are also provided in this paper. This is the first study on the MATE genes in mangroves and the results provide comprehensive information on the molecular mechanisms enabling the survival of mangroves under hostile conditions.

High-Efficiency Plasma Source Using a Magnetic Mirror Trap for Miniature-Ion Pumps.

In this study, we design a highly efficient plasma source using a magnetic mirror trap with two opposing permanent magnets for a miniature high-efficiency ion pump. First, we simulated the distribution of the magnetic field line formed by the proposed magnetic mirror configuration. By optimizing the distance between two opposing permanent magnets and size of these magnets, a magnetic mirror ratio value of 27 could be obtained, which is an electron confinement efficiency of over 90%. We also conducted an experiment on a high-efficiency discharge plasma source for a miniature ion pump using an optimized magnetic circuit. As a result, we revealed that the proposed magnetic circuit has a pronounced effect on plasma generation, particularly in the high-vacuum region.

Protein dynamics of a light-driven Na+ pump rhodopsin probed using a tryptophan residue near the retinal chromophore.

Direct observation of protein structural changes during ion transport in ion pumps provides valuable insights into the mechanism of ion transport. In this study, we examined structural changes in the light-driven sodium ion (Na+) pump rhodopsin KR2 on the sub-millisecond time scale, corresponding with the uptake and release of Na+. We compared the ion-pumping activities and transient absorption spectra of WT and the W215F mutant, in which the Trp215 residue located near the retinal chromophore on the cytoplasmic side was replaced with a Phe residue. Our findings indicated that atomic contacts between the bulky side chain of Trp215 and the C20 methyl group of the retinal chromophore promote relaxation of the retinal chromophore from the 13-cis to the all-trans form. Since Trp215 is conserved in other ion-pumping rhodopsins, the present results suggest that this residue commonly acts as a mechanical transducer. In addition, we measured time-resolved ultraviolet resonance Raman (UVRR) spectra to show that the environment around Trp215 becomes less hydrophobic at 1 ms after photoirradiation and recovers to the unphotolyzed state with a time constant of around 10 ms. These time scales correspond to Na+ uptake and release, suggesting evolution of a transient ion channel at the cytoplasmic side for Na+ uptake, consistent with the alternating-access model of ion pumps. The time-resolved UVRR technique has potential for application to other ion-pumping rhodopsins and could provide further insights into the mechanism of ion transport.

Bioinspired Artificial Ion Pumps.

Ion pumps are important membrane-spanning transporters that pump ions against the electrochemical gradient across the cell membrane. In biological systems, ion pumping is essential to maintain intracellular osmotic pressure, to respond to external stimuli, and to regulate physiological activities by consuming adenosine triphosphate. In recent decades, artificial ion pumping systems with diverse geometric structures and functions have been developing rapidly with the progress of advanced materials and nanotechnology. In this Review, bioinspired artificial ion pumps, including four categories: asymmetric structure-driven ion pumps, pH gradient-driven ion pumps, light-driven ion pumps, and electron-driven ion pumps, are summarized. The working mechanisms, functions, and applications of those artificial ion pumping systems are discussed. Finally, a brief conclusion of underpinning challenges and outlook for future research are tentatively discussed.