Artificial Ion Channels Research Articles

Naphthalene Diimide-Based Metallacage as an Artificial Ion Channel for Chloride Ion Transport.

Developing synthetic molecular devices for controlling ion transmembrane transport is a promising research field in supramolecular chemistry. These artificial ion channels provide models to study ion channel diseases and have huge potential for therapeutic applications. Compared with self-assembled ion channels constructed by intermolecular weak interactions between smaller molecules or cyclic compounds, metallacage-based ion channels have well-defined structures and can exist as single components in the phospholipid bilayer. A naphthalene diimide-based artificial chloride ion channel is constructed through efficient subcomponent self-assembly and its selective ion transport activity in large unilamellar vesicles and the planar lipid bilayer membrane by fluorescence and ion-current measurements is investigated. Molecular dynamics simulations and density functional theory calculations show that the metallacage spans the entire phospholipid bilayer as an unimolecular ion transport channel. This channel transports chloride ions across the cell membrane, which disturbs the ion balance of cancer cells and inhibits the growth of cancer cells at low concentrations.

Ultrahigh Lithium Selective Transport in Two-Dimensional Confined Ice.

Inspired by selective ion transport in biological membrane proteins, researchers developed artificial ion channels that sieve monovalent cations, catering to the increasing lithium demand. In this work, we engineered an ion transport channel based on the confined ice within two-dimensional (2D) capillaries and found that the permselectivity of monovalent cations depends on the anisotropy of the confined ice. Particularly, the 2D confined ice showed an anomalous lithium selective transport along the (002) direction in the vermiculite capillary, with the Li+/Na+ and Li+/K+ permselectivity reaching up to 556 ± 86 and 901 ± 172, respectively, superior to most ion-selective channels. However, the 2D confined ice along the (100) direction showed less Li+ permselectivity. Additionally, the anisotropy of 2D confined ice can be tuned by adjusting the interlayer spacing. By providing insights into the ion transport in the 2D confined ice, our work may inspire more design of monovalent ion-selective channels for efficient lithium separation.

Unveiling the transport of water and ions in the nanocage of zeolitic imidazolate frameworks by molecular dynamics

Precise ion/water and ion/ion separation requires pores of size closely aligned with the dimension of filtering molecules or ions. Zeolitic imidazolate frameworks (ZIFs), a class of porous crystallizes with well-defined Å ngstrom pores and diverse structures, making them promising candidates for nanofluidic channels. In this work, we perform molecular simulations to explore the structures and kinetics of water and ions confined in 4 typical ZIFs, including ZIF-65, ZIF-8, SALEM-2 and ZIF-Cl. Our findings reveal that the structure of water molecules within these ZIFs closely resembles that of bulk water but two diffusion regimes are identified. Notably, the diffusion coefficients (D) of the water are one order of magnitude lower than bulk water while the order of D for different ZIFs cannot be simply attributed to steric effects. The ion diffusion barriers exhibit a distinct contrast between monovalent and divalent cations, closely mirroring ion-valence selectivity as biological channels. Additionally, the Å ngstrom-scale pores within ZIFs demonstrate exceptional capability of filtering alkali metal ions with the selectivity as high as 10–100. Further analysis underscores the substantial effects of pore flexibility. The comprehensive simulation results strongly indicate that ZIFs hold significant promise for utilization in development of artificial ion channels and precise ion separation membranes.

Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression

Combined activation of artificial and natural ion channels for disrupting mitochondrial ion homeostasis towards effective postoperative tumor recurrence and metastasis suppression

A unimolecular artificial cation channel based on cascaded hydrated acid groups.

A cation channel possessing cascaded hydrated acid groups has been successfully constructed using pillar[5]arene integrated with dual cyclodextrins. As a proof-of-concept, the secondary side of cyclodextrin substituted by 24 -CO2H groups presents high coordination sites, which helps hydrated cations to quickly dehydrate and accelerates efficient cation transport (Rb+ > Cs+ > K+ > Na+ > Li+). Notably, benefitted by the protonation and deprotonation of -CO2H groups, ion permeation activity of the channel molecules under acidic condition (pH = 6.0) is 2.8 times higher than that under alkaline conditions (pH = 8.0), exhibiting pH-modulated property and promising potential in building intelligent artificial ion channels with customized features.

Dynamic asymmetric mechanical responsive carbon nanotube fiber for ionic logic gate

Inspired by biological ion channels, numerous artificial asymmetric ion channels have been synthesized to facilitate the fabrication of ionic circuits. Nevertheless, the creation of biomimetic asymmetric ion channels necessitates expensive scientific apparatus and intricate material processing procedures, which constrains its advancement within the realm of ionic devices. In this study, we have devised dynamic asymmetric ion channels with mechanical responsiveness by combining polymers of varying elastic modulus along the longitudinal axis of carbon nanotube fiber (CNTF). The ion rectification can be modulated via the disparate response of CNTF-based ion channels to mechanical stress. We have effectively employed these asymmetric ion channels with mechanical sensitivity in the design of a logic gate device, achieving logic operations such as “AND” and “OR”. The conception of these dynamic asymmetric ion channels with mechanical sensitivity offers a straightforward, cost-effective, and versatile approach for generating ion channels, highlighting their potential application in intricate, highly integrated ionic circuits.

Nanoscale one-dimensional close packing of interfacial alkali ions driven by water-mediated attraction.

The permeability and selectivity of biological and artificial ion channels correlate with the specific hydration structure of single ions. However, fundamental understanding of the effect of ion-ion interaction remains elusive. Here, via non-contact atomic force microscopy measurements, we demonstrate that hydrated alkali metal cations (Na+ and K+) at charged surfaces could come into close contact with each other through partial dehydration and water rearrangement processes, forming one-dimensional chain structures. We prove that the interplay at the nanoscale between the water-ion and water-water interaction can lead to an effective ion-ion attraction overcoming the ionic Coulomb repulsion. The tendency for different ions to become closely packed follows the sequence K+ > Na+ > Li+, which is attributed to their different dehydration energies and charge densities. This work highlights the key role of water molecules in prompting close packing and concerted movement of ions at charged surfaces, which may provide new insights into the mechanism of ion transport under atomic confinement.

Evolution of artificial ion channels.

Evolution of artificial ion channels.

Designing artificial ion channels with strict K+/Na+ selectivity toward next-generation electric-eel-mimetic ionic power generation.

A biological potassium channel is >1000 times more permeable to K+ than to Na+ and exhibits a giant permeation rate of ∼108 ions/s. It is a great challenge to construct artificial potassium channels with such high selectivity and ion conduction rate. Herein, we unveil a long-overlooked structural feature that underpins the ultra-high K+/Na+ selectivity. By carrying out massive molecular dynamics simulation for ion transport through carbonyl-oxygen-modified bi-layer graphene nanopores, we find that the twisted carbonyl rings enable strict potassium selectivity with a dynamic K+/Na+ selectivity ratio of 1295 and a K+ conduction rate of 3.5×107 ions/s, approaching those of the biological counterparts. Intriguingly, atomic trajectories of K+ permeation events suggest a dual-ion transport mode, i.e. two like-charged potassium ions are successively captured by the nanopores in the graphene bi-layer and are interconnected by sharing one or two interlayer water molecules. The dual-ion behavior allows rapid release of the exiting potassium ion via a soft knock-on mechanism, which has previously been found only in biological ion channels. As a proof-of-concept utilization of this discovery, we propose a novel way for ionic power generation by mixing KCl and NaCl solutions through the bi-layer graphene nanopores, termed potassium-permselectivity enabled osmotic power generation (PoPee-OPG). Theoretically, the biomimetic device achieves a very high power density of >1000W/m2 with graphene sheets of <1% porosity. This study provides a blueprint for artificial potassium channels and thus paves the way toward next-generation electric-eel-mimetic ionic power generation.

DNA nanopores as artificial membrane channels for bioprotonics

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner.

Ultra-mechanosensitive Chloride Ion Transport through Bioinspired High-Density Elastomeric Nanochannels.

Mechanosensitive ion channels play crucial roles in physiological activities, where small mechanical stimuli induce the membrane tension, trigger the ion channels' deformation, and are further transformed into significant electrochemical signals. Artificial ion channels with stiff moduli have been developed to mimic mechanosensory behaviors, exhibiting an electrochemical response by the high-pressure-induced flow. However, fabricating flexible mechanosensitive channels capable of regulating specific ion transporting upon dramatic deformation has remained a challenge. Here, we demonstrate bioinspired high-density elastomeric channels self-assembled by polyisoprene-b-poly4-vinylpyridine, which exhibit ultra-mechanosensitive chloride ion transport resulting from nanochannel deformation. The PI-formed continuous elastic matrix can transmit external forces into internal tensions, while P4VP forms transmembrane chloride channels that undergo dramatic deformation and respond to mechanical stimuli. The integrated and flexible chloride channels present a dramatic and stable electrochemical signal toward a low pressure of 0.2 mbar. This research first demonstrates the artificial mechanosensory chloride channels, which could provide a promising avenue for designing flexible and responsive channel systems.

Probing the Ion Transport Properties of Ultrashort Carbon Nanotubes Integrated with Supported Lipid Bilayers via Electrochemical Analysis.

Supported lipid bilayers (SLBs) are commonly used to investigate interactions between cell membranes and their environment. These model platforms can be formed on electrode surfaces and analyzed using electrochemical methods for bioapplications. Carbon nanotube porins (CNTPs) integrated with SLBs have emerged as promising artificial ion channel platforms. In this study, we present the integration and ion transport characterization of CNTPs in in vivo environments. We combine experimental and simulation data obtained from electrochemical analysis to analyze the membrane resistance of the equivalent circuits. Our results show that carrying CNTPs on a gold electrode results in high conductance for monovalent cations (K+ and Na+) and low conductance for divalent cations (Ca2+).

A self-powered hybridized sensor inspired by human skin for mimicking fast and slow adaptation

Four types of mechanoreceptors in human skin are capable of sensing different stimuli and transmitting fast adapting (FA) and slow adapting (SA) signals to the brain. To mimic these functions, novel devices have been developed by coupling multiple sensing principles. However, complicated fabrication, high minimum detection limit, and low sensitivity hinder their wide application. In this paper, we report a self-powered mechanical stimulus receptor based on a combination of an artificial ion channel system, a single-electrode triboelectric nanogenerator, and a parallel plate capacitor, which can mimic human skin to monitor both dynamic and static stimuli. The introduction of the capacitive sensing part of this sensor overcomes the problem of conventional potentiometric sensors that are unable to monitor static stimuli due to insufficient electrolyte deformation at low pressure. This device detects external mechanical stimuli with high sensitivity (2.75 kPa−1 under dynamics and 1.18 kPa−1 under statics) and low detection limits (19.5 Pa). For the feasibility study, the signal simulation of Morse code is successfully implemented. In addition, the sensor has been shown to be able to detect human joint activity. This new sensor provides more options for future wearable electronic devices and human–computer interfaces.

Highly active artificial potassium channels having record-high K+/Na+ selectivity of 20.1

Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task. In this work, we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels, alongside with boosted ion transport activities. More specifically, two types of mutually compatible sterically bulky groups (benzo-crown ether and tert‑butyl group) were appended onto a monopeptide-based scaffold, which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure. Strong steric repulsions among the same type of bulky groups (either benzo-crown ethers or tert‑butyl groups), which are forced into proximity by H-bonds, favor the formation of hetero-oligomeric ensembles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert‑butyl groups, rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert‑butyl groups. Coupled with side chain tuning, this social self-sorting strategy delivers highly active hetero-oligomeric K+-selective ion channel (5F12‧BF12)n, displaying the highest K+/Na+ selectivity of 20.1 among artificial potassium channels and an excellent EC50 value of 0.50 µmol/L (0.62 mol% relative to lipids) in terms of single channel concentration

Integrating Ion Channels with Bioelectronics for Biotic–Abiotic Systems

Precise and highly regulated flow of biomolecules and ions through complex cellular networks is crucial for communication and information processing in living systems. In contrast, human‐made electronics rely on the flow of electrons and holes through well‐defined semiconductor networks for processing. Ion channels play vital roles in regulating the flow of ions and biomolecules across the cell membrane with a complexity unmatched in any semiconductor device. To enable biotic–abiotic communication and leverage this complexity, supported lipid bilayers (SLBs) create a planar cell membrane for integration with bioelectronics. This review discusses the integration of ion channels in bioelectronic devices for biotic–abiotic communication with enhanced functionality. This review begins with an introduction of natural and artificial ion channels across SLBs, continues with a description of bioelectronic devices integrating SLBs, and concludes with examples of functional ion channel bioelectronics.

Artificial Action Potential and Ionic Power Device Inspired by Ion Channels and Excitable Cell.

In vivo, the membrane potential of the excitable cell working by ion gradients plays a significant role in bioelectricity generation and nervous system operation. Conventional bioinspired power systems generally have adopted ion gradients, but overlook the functions of ion channels and Donnan effect to generate efficient ion flow in the cell. Here, cell-inspired ionic power device implementing the Donnan effect using multi-ions and monovalent ion exchange membranes as artificial ion channels is realized. Different ion-rich electrolytes on either side of the selective membrane generate the ion gradient potentials with high ionic currents and reduce the osmotic imbalance of the membrane. Based on this device, the artificial neuronal signaling is presented by the mechanical switching system of the ion selectivity like mechanosensitive ion channels in a sensory neuron. Compared with reverse electrodialysis, which requires a low concentration, a high-power device with ten times the current and 8.5 times the power density is fabricated. This device activates grown muscle cells by increasing power through serial connection like an electric eel, and shows the possibility of an ion-based artificial nervous system.

A Benzohydrazide-Based Artificial Ion Channel that Modulates Chloride Ion Concentration in Cancer Cells and Induces Apoptosis by Disruption of Autophagy.

Fluctuations in the intracellular chloride ion concentration, mediated by synthetic ion transporters, have been known to induce cytotoxicity in cells by disrupting ionic homeostasis. However, the activity of these transporters in modulating autophagy remains largely unexplored. Here, we report a benzoylbenzohydrazide (1c) that self-assembles to form a supramolecular nanochannel lumen that allows selective and efficient transport of chloride ions across the cell membranes, disrupts ion homeostasis, and thus leads to the induction of apoptosis in cancer cells. It is important to note that the transporter was relatively nontoxic to cells of noncancerous origin. 1c was also shown to induce the deacidification of lysosomes, thereby disrupting autophagy in cancer cells. Taken together, these findings provide a rare example of an artificial ion channel that specifically targets cancer cells by induction of apoptosis via disruption of autophagy.

Crown Ether-Based Ion Transporters in Bilayer Membranes.

Bilayer membranes that enhance the stability of the cell are essential for cell survival, separating and protecting the interior of the cell from its external environment. Membrane-based channel proteins are crucial for sustaining cellular activities. However, dysfunction of these proteins would induce serial channelopathies, which could be substituted by artificial ion channel analogs. Crown ethers (CEs) are widely studied in the area of artificial ion channels owing to their intrinsic host-guest interaction with different kinds of organic and inorganic ions. Other advantages such as lower price, chemical stability, and easier modification also make CE a research hotspot in the field of synthetic transmembrane nanopores. And numerous CEs-based membrane-active synthetic ion channels were designed and fabricated in the past decades. Herein, the recent progress of CEs-based synthetic ion transporters has been comprehensively summarized in this review, including their design principles, functional mechanisms, controllable properties, and biomedical applications. Furthermore, this review has been concluded by discussing the future opportunities and challenges facing this research field. It is anticipated that this review could offer some inspiration for the future fabrication of novel CEs-derived ion transporters with more advanced structures, properties, and practical applications.

Co-Assembly of Carbon Nanotube Porins into Biomimetic Peptoid Membranes.

Robust and cost-effective membrane-based separations are essential to solving many global crises, such as the lack of clean water. Even though the current polymer-based membranes are widely used for separations, their performance and precision can be enhanced by using a biomimetic membrane architecture that consists of highly permeable and selective channels embedded in a universal membrane matrix. Researchers have shown that artificial water and ion channels, such as carbon nanotube porins (CNTPs), embedded in lipid membranes can deliver strong separation performance. However, their applications are limited by the relative fragility and low stability of the lipid matrix. In this work,wedemonstrate that CNTPs can co-assemble into twodimension(2D) peptoid membrane nanosheets, opening up a way to produce highly programmable synthetic membranes with superior crystallinity and robustness. A combination of molecular dynamics (MD) simulations, Ramanspectroscopy, X-ray diffraction(XRD), and atomicforcemicroscopy(AFM) measurements to verify the co-assembly of CNTP and peptoids are used and show that it does not disrupt peptoid monomer packing within the membrane. These results provide a new option for designing affordable artificial membranes and highly robust nanoporous solids.

An artificial sodium-selective subnanochannel

Single-ion selectivity with high precision has long been pursued for fundamental bioinspired engineering and applications such as in ion separation and energy conversion. However, it remains a challenge to develop artificial ion channels to achieve single-ion selectivity comparable to their biological analogs, especially for high Na+/K+ selectivity. Here, we report an artificial sodium channel by subnanoconfinement of 4'-aminobenzo-15-crown-5 ethers (15C5s) into ~6-Å-sized metal-organic framework subnanochannel (MOFSNC). The resulting 15C5-MOFSNC shows an unprecedented Na+/K+ selectivity of tens to 102 and Na+/Li+ selectivity of 103 under multicomponent permeation conditions, comparable to biological sodium channels. A co-ion-responsive single-file transport mechanism in 15C-MOFSNC is proposed for the preferential transport of Na+ over K+ due to the synergetic effects of size exclusion, charge selectivity, local hydrophobicity, and preferential binding with functional groups. This study provides an alternative strategy for developing potential single-ion selective channels and membranes for many applications.