Biological Ion Channels Research Articles

Water inside the Selectivity Filter of a K+ Ion Channel: Structural Heterogeneity, Picosecond Dynamics, and Hydrogen Bonding.

Water inside biological ion channels regulates the key properties of these proteins, such as selectivity, ion conductance, and gating. In this article, we measure the picosecond spectral diffusion of amide I vibrations of an isotope-labeled KcsA potassium channel using two-dimensional infrared (2D IR) spectroscopy. By combining waiting time (100-2000 fs) 2D IR measurements of the KcsA channel including 13C18O isotope-labeled Val76 and Gly77 residues with molecular dynamics simulations, we elucidated the site-specific dynamics of water and K+ ions inside the selectivity filter of KcsA. We observe inhomogeneous 2D line shapes with extremely slow spectral diffusion. Our simulations quantitatively reproduce the experiments and show that water is the only component with any appreciable dynamics, whereas K+ ions and the protein are essentially static on a picosecond timescale. By analyzing simulated and experimental vibrational frequencies, we find that water in the selectivity filter can be oriented to form hydrogen bonds with adjacent or nonadjacent carbonyl groups with the reorientation timescales being three times slower and comparable to that of water molecules in liquid, respectively. Water molecules can reside in the cavity sufficiently far from carbonyls and behave essentially like "free" gas-phase-like water with fast reorientation times. Remarkably, no interconversion between these configurations was observed on a picosecond timescale. These dynamics are in stark contrast with liquid water, which remains highly dynamic even in the presence of ions at high concentrations.

Anomalously enhanced ion transport and uptake in functionalized angstrom-scale two-dimensional channels.

Emulating angstrom-scale dynamics of the highly selective biological ion channels is a challenging task. Recent work on angstrom-scale artificial channels has expanded our understanding of ion transport and uptake mechanisms under confinement. However, the role of chemical environment in such channels is still not well understood. Here, we report the anomalously enhanced transport and uptake of ions under confined MoS2-based channels that are ~five angstroms in size. The ion uptake preference in the MoS2-based channels can be changed by the selection of surface functional groups and ion uptake sequence due to the interplay between kinetic and thermodynamic factors that depend on whether the ions are mixed or not prior to uptake. Our work offers a holistic picture of ion transport in 2D confinement and highlights ion interplay in this regime.

Supralinear scaling behavior of ionic transport in membrane nanochannels regulated by outer-surface charges.

The peculiarity of ion transport at the nanoscale is revealed through electrophysiological studies of two biological ion channels: the cation-selective bacterial porin-OmpF and the mitochondrial voltage-dependent anion channel (VDAC). We provide evidence of an unprecedented scaling behavior in the power-law relationship between conductivity and concentration G ∼ c α with α > 1 when functional groups attached to the pore inner wall have opposite charges to those located in the nanochannel's outer surface. Indeed, we find α ∼ 1.4 both for OmpF in positively charged membranes and for VDAC in negatively charged ones. The experiments are analyzed using different levels of theoretical models, starting with an equivalent circuit where total electrical current is described as the sum of ionic currents. Subsequently, we show that electrical circuits incorporating simplifying assumptions such as local electroneutrality and Donnan equilibrium consistently account for the measured G-c relationships yielding extremely similar results to the numerical results of structure-based Poisson-Nernst-Planck equations computed without these assumptions. We demonstrate that unexpected scaling exponents do not correspond to deviations from these classical equilibrium/electroneutrality assumptions, but rather to the structural features of the pore that are not included in oversimplified models in terms of shape and/or charge distribution. In contrast to the predictions of widely accepted models, we demonstrate both experimentally and theoretically that the conductance of ion-selective nanochannels can be drastically reduced in dilute solutions through a mechanism in which membrane charges and pore charges do not compensate for each other but act as interacting sites of opposite charge. Our insights into the critical role of external surface charges aim to open new conceptual avenues for developing nanofluidic devices with enhanced capabilities for energy conversion and sensing properties.

Advances in nanofluidic field-effect transistors: external voltage-controlled solid-state nanochannels for stimulus-responsive ion transport and beyond.

Ion channels, intricate protein structures facilitating precise ion passage across cell membranes, are pivotal for vital cellular functions. Inspired by the remarkable capabilities of biological ion channels, the scientific community has ventured into replicating these principles in fully abiotic solid-state nanochannels (SSNs). Since the gating mechanisms of SSNs rely on variations in the physicochemical properties of the channel surface, the modification of their internal architecture and chemistry constitutes a powerful strategy to control the transport properties and, consequently, render specific functionalities. In this framework, both the design of the nanofluidic platform and the subsequent selection and attachment of different building blocks gain special attention. Similar to biological ion channels, functional SSNs offer the potential to finely modulate ion transport in response to various stimuli, leading to innovations in a variety of fields. This comprehensive review delves into the intricate world of ion transport across stimuli-responsive SSNs, focusing on the development of external voltage-controlled nanofluidic devices. This kind of field-effect nanofluidic technology has attracted special interest due to the possibility of real-time reconfiguration of the ion transport with a non-invasive strategy. These properties have found interesting applications in drug delivery, biosensing, and nanoelectronics. This document will address the fundamental principles of ion transport through SSNs and the construction, modification, and applications of external voltage-controlled SSNs. It will also address future challenges and prospects, offering a comprehensive perspective on this evolving field.

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.

Biosensing with Tailored Track-Etched Nanochannels

Inspired by the high sensitivity, efficiency and selectivity of biological ion channels, the development of solid-state nanochannel sensors has been at the forefront of nanotechnology research in the last years. Many researchers worldwide have concentrated their efforts on the development of artificial nanochannels that can mimic the features of biological ion channels. These synthetic nanostructures are based on abiotic materials which provide higher robustness, thermal stability, chemical versatility and mechanical resistance than their biological counterparts. Furthermore, synthetic nanochannels and specific surface functionalization strategies have enabled fine control over the geometry and charge distribution which yielded the ability to manipulate the flux of ions through the channel. This gave rise to the formation of nanochannel-based platforms with applications in (bio)sensing as well as other fields. The development of chemical- and biosensors requires a combination of reliable nanofabrication techniques and versatile surface modification strategies, which render high sensitivity and high selectivity, respectively [1].Tailored single polymer nanochannels are routinely fabricated by ion-track nanotechnology. Polymer films are first irradiated with individual swift heavy ions at the GSI UNILAC accelerator. Each ion generates a highly localized cylindrical damage zone along its trajectory. These so-called ion tracks are subsequently dissolved and enlarged in a chemical etching process. By selecting suitable etching conditions, geometry (cylindrical, conical or bullet-like) and size of the nanochannels can be adjusted. The nanochannel surface can then be functionalized by means of different chemical strategies to enhance the sensing capabilities.There are two main nanochannel sensing techniques, ion current rectification (ICR) and resistive-pulse sensing (RPS). Both are affected by the geometry and surface charge of the nanochannel and based on measuring the change in ion current flowing through the channel induced by the chosen analyte [2]. In both approaches, the presence of a target analyte triggers a variation in the physicochemical properties of the channel which can be related to measurable changes in the transmembrane current, and is proportional to the analyte concentration.In this contribution, we will present nanochannel sensing platforms based on several single polymer channels fabricated by ion-track nanotechnology and a selection of surface functionalization strategies applied to the nanochannels. We will then discuss selected examples recently obtained with these tailored functionalized nanochannels and demonstrate selective and sensitive sensing applications based on both the ICR and RPS phenomena.[1] Toum Terrones, Y., Cayón, V. M., Laucirica, G., Cortez, M. L., Toimil-Molares, M. E., Trautmann, C., ... & Azzaroni, O. (2022). Ion Track-Based Nanofluidic Biosensors. In Miniaturized Biosensing Devices: Fabrication and Applications (pp. 57-81). Singapore: Springer Nature Singapore.[2] Kaya, D., & Keçeci, K. (2020). Track-etched nanoporous polymer membranes as sensors: A review. Journal of The Electrochemical Society, 167(3), 037543.

Modular Gating of Ion Transport by Postsynthetic Charge Transfer Complexation in a Metal-Organic Framework.

Nature's design of biological ion channels that demonstrates efficient gating and selectivity brings to light a very promising model to mimic and design for achieving selective and tunable ion transport. Functionalized nanopores that permit modulation of the pore wall charges are a compelling approach to gain control over the ion transport mechanism through the pores. This makes way for employing a noncovalent supramolecular approach for attaining charge reversal of the MOF pore walls using donor-acceptor pairs that can demonstrate strong charge transfer interactions. Herein, robust Zr4+-based mesoporous MOF-808 was postsynthetically modified into an anion-selective nanochannel (MOF-808-MV) by modification with dicationic viologen-based motifs. Charge modulation and even reversal of the MOF-808-MV pore walls were then explored taking advantage of strong charge transfer interactions between the grafted dicationic viologen acceptor moieties and anionic, π-electron-rich donor guest molecules such as pyranine (PYR) and tetrathiafulvalene tetrabenzoic acid (TTF-TA). Tunability of the MOF pore charge from positive to neutral to negative was achieved via simple methodologies such as diffusion control in case of guest molecule like PYR and by pH modulation for pH-responsive guest like TTF-TA. This results in a concomitant modulation in the selectivity of the nanochannel, rendering it from anion-selective to ambipolar to cation-selective. Furthermore, as a real-time application of this ion channel, Na+ ion conductivity (σ = 3.5 × 10-5 S cm-1) was studied at ambient temperature.

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.

Artificial Sodium Channels for Enhanced Osmotic Energy Harvesting.

Inspired by the ion channels of electric eels, we can use biomimetic nanofluidic materials to harvest the osmotic power released by mixing seawater and river water. While biological ion channels have both cation/anion and inter-cation selectivity, previous nanofluidic materials neglected the latter. As a result, NaCl solutions were generally used to simulate river water, ignoring the fact that the dominating cation in river water is typically Ca2+. In this work, we show that the different ionic compositions of seawater and river water can be exploited to improve osmotic power density by employing biomimetic sodium selective materials. Inspired by a range of properties of biological sodium channels, we constructed artificial sodium channels with zeolitic imidazolate framework-65 crystals, which selectively transport Na+ but almost completely block Ca2+. Resultantly, the effective concentration gradient of seawater/river water is dramatically increased by preventing the major cations in the river water from participating in the ion diffusion. As a result, the osmotic power density can be increased by more than 1 order of magnitude. These results should open new avenues to develop high-performance osmotic generators and may advance other applications based on biomimetic ion channels such as neuromorphic information processing.

Synaptical Tunability of Multipore Nanofluidic Memristors.

We demonstrate a multipore nanofluidic memristor with conical pores showcasing a wide range of hysteresis and memristor properties that provide functionalities for brainlike computation in neuromorphic applications. Leveraging the interplay between the charged functional groups on the pore surfaces and the confined ionic solution, the memristor characteristics are modulated through the electrolyte type, ionic concentrations, and pH levels of the aqueous solution. The multipore membrane mimics the functional characteristics of biological ion channels and displays synaptical potentiation and depression. Furthermore, this property can be inverted in polarity by chemically varying the pH level. The ability to modulate memory effects by ionic conductivity holds promise for enhancing signal information processing capabilities.

Covalently Functionalized Nanopores for Highly Selective Separation of Monovalent Ions.

Biological ion channels possess prominent ion transport performances attributed to their critical chemical groups across the continuous nanoscale filters. However, it is still a challenge to imitate these sophisticated performances in artificial nanoscale systems. Herein, this work develops the strategy to fabricate functionalized graphene nanopores in pioneer based on the synergistic regulation of the pore size and chemical properties of atomically thin confined structure through decoupling etching combined with in situ covalent modification. The modified graphene nanopores possess asymmetric ion transport behaviors and efficient monovalent metal ions sieving (K+ /Li+ selectivity ≈48.6). Meanwhile, it also allows preferential transport for cations, the resulting membranes exhibit a K+ /Cl- selectivity of 76 and a H+ /Cl- selectivity of 59.3. The synergistic effects of steric hindrance and electrostatic interactions imposing a higher energy barrier for Cl- or Li+ across nanopores lead to ultra-selective H+ or K+ transport. Further, the functionalized graphene nanopores generate a power density of 25.3W m-2 and a conversion efficiency of 33.9%, showing potential application prospects in energy conversion. The theoretical studies quantitatively match well with the experimental results. The feasible preparation of functionalized graphene nanopores paves the way toward direct investigation on ion transport mechanism and advanced design in devices.

Confirming Silent Translocation through Nanopores with Simultaneous Single-Molecule Fluorescence and Single-Channel Electrical Recordings.

Most of what is known concerning the luminal passage of materials through nanopores arises from electrical measurements. Whether nanopores are biological, solid-state, synthetic, hybrid, glass-capillary-based, or protein ion channels in cells and tissues, characteristic signatures embedded in the flow of ionic current are foundational to understanding functional behavior. In contrast, this work describes passage through a nanopore that occurs without producing an electrical signature. We refer to the phenomenon as "silent translocation." By definition, silent translocations are invisible to the standard tools of electrophysiology and fundamentally require a simultaneous ancillary measurement technique for positive identification. As a result, this phenomenon has been largely unexplored in the literature. Here, we report on a derivative of Cyanine 5 (sCy5a) that passes through the α-hemolysin (αHL) nanopore silently. Simultaneously acquired single-molecule fluorescence and single-channel electrical recordings from bilayers formed over a closed microcavity demonstrate that translocation does indeed take place, albeit infrequently. We report observations of silent translocation as a function of time, dye concentration, and nanopore population in the bilayer. Lastly, measurement of the translocation rate as a function of applied potential permits estimation of an effective energy barrier for transport through the pore as well as the effective charge on the dye, all in the absence of an information-containing electrical signature.

Transcendent Aspects of Proton Channels.

A handful of biological proton-selective ion channels exist. Some open at positive or negative membrane potentials, others open at low or high pH, and some are light activated. This review focuses on common features that result from the unique properties of protons. Proton conduction through water or proteins differs qualitatively from that of all other ions. Extraordinary proton selectivity is needed to ensure that protons permeate and other ions do not. Proton selectivity arises from a proton pathway comprising a hydrogen-bonded chain that typically includes at least one titratable amino acid side chain. The enormously diverse functions of proton channels in disparate regions of the phylogenetic tree can be summarized by considering the chemical and electrical consequences of proton flux across membranes. This review discusses examples of cells in which proton efflux serves to increase pHi, decrease pHo, control the membrane potential, generate action potentials, or compensate transmembrane movement of electrical charge.

Sonochemical Synthesis and Ion Transport Properties of Surfactant-Stabilized Carbon Nanotube Porins.

Carbon nanotube porins (CNTPs), short segments of carbon nanotubes stabilized by a lipid coating, are a promising example of artificial membrane channels that mimic a number of key behaviors of biological ion channels. While the lipid-assisted synthesis of CNTPs may facilitate their subsequent incorporation into lipid bilayers, it limits the applicability of these pores in other self-assembled membrane materials and also precludes the use of large-scale purified CNT feedstocks. Here we demonstrate that CNTPs can be synthesized by sonochemical cutting of long CNT feedstocks in the presence of different surfactants, producing CNTS with transport properties identical with those obtained by the lipid-assisted procedure. Our results open up a wide variety of synthetic routes for CNTP production.

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.

Development of Mixed Matrix Membranes with Penetrating Subnanochannels for Efficient Molecule/Ion Separation

AbstractMembrane‐based separation technologies are becoming increasingly prominent in many important industrial separation applications. In the past decade, nanoporous materials, as promising filler components for high‐performance mixed matrix membranes (MMMs), have seen a boom given the merits of remarkable chemical and structural variability. However, it remains challenging to address the trade‐off effect of MMMs between molecular/ionic selectivity and permeability. Biological ion channels that penetrate through cell membranes have provided new insights for the construction of novel structures of MMMs. In recent years, MMMs with cell membrane‐like structures have gained much attention and achieved significant progress in the field of separation. In this minireview, recent advances in the design and construction of MMMs with penetrating subnanochannels are summarized. After that, the applications of these MMMs with penetrating subnanochannels in gas separation and ion sieving are highlighted and discussed in detail. Finally, the future developments and challenges for the MMMs with penetrating subnanochannels are prospected.

Two-Dimensional Graphene-Based Potassium Channels Built at an Oil/Water Interface.

Graphene-based laminar membranes exhibit remarkable ion sieving properties, but their monovalent ion selectivity is still low and much less than the natural ion channels. Inspired by the elementary structure/function relationships of biological ion channels embedded in biomembranes, a new strategy is proposed herein to mimic biological K+ channels by using the graphene laminar membrane (GLM) composed of two-dimensional (2D) angstrom(Å)-scale channels to support a simple model of semi-biomembrane, namely oil/water (O/W) interface. It is found that K+ is strongly preferred over Na+ and Li+ for transferring across the GLM-supported water/1,2-dichloroethane (W/DCE) interface within the same potential window (-0.1-0.6 V), although the monovalent ion selectivity of GLM under the aqueous solution is still low (K+/Na+~1.11 and K+/Li+~1.35). Moreover, the voltammetric responses corresponding to the ion transfer of NH4+ observed at the GLM-supported W/DCE interface also show that NH4+ can often pass through the biological K+ channels due to their comparable hydration-free energies and cation-π interactions. The underlying mechanism of as-observed K+ selective voltammetric responses is discussed and found to be consistent with the energy balance of cationic partial-dehydration (energetic costs) and cation-π interaction (energetic gains) as involved in biological K+ channels.

Electronegative Nanochannels Accelerating Lithium‐Ion Transport for Enabling Highly Stable and High‐Rate Lithium Metal Anodes

AbstractAchieving a high Li+ transference number is an effective strategy to inhibit the nucleation of lithium dendrites on the metal anode according to classical Sand's time principle. However, improving the Li+ transference number usually causes aloss of ionic conductivity of lithium metal batteries. Here, inspired by biological ion channels tuning ion transport, an electronegative nanochannels separator is developed to accelerate Li+ transport for enabling dendrite‐free and high‐rate lithium metal anodes. Benefiting from selective and fast Li+ transport, the electronegative nanochannels separator can simultaneously achieve high Li+ transference number (0.77) and high Li+ conductivity (1.36 mS cm−2) within a liquid lithium metal battery. Such an optimization of Li+ transport dynamics can significantly prolong the nucleation time of lithium dendrite and thus effectively suppress dendritic growth, which contributes to an extremely stable Li plating/stripping cycling for over 2000 h at a high current density of 5 mA cm−2. When assembled into lithium metal batteries, the electronegative nanochannels separator enables superior comprehensive electrochemical performance compared with the commercial polyolefin one. This work provides new insights into the design of functional separators toward dendrite‐free and high‐rate liquid lithium metal batteries.

Multi-Stimuli-Responsive and Mechano-Actuated Biomimetic Membrane Nanopores Self-Assembled from DNA.

In bioinspired design, biological templates are mimicked in structure and function by highly controllable synthetic means. Of interest are static barrel-like nanopores that enable molecular transport across membranes for use in biosensing, sequencing, and biotechnology. However, biological ion channels offer additional functions such as dynamic changes of the entire pore shape between open and closed states, and triggering of dynamic processes with biochemical and physical stimuli. To better capture this complexity, this report presents multi-stimuli and mechano-responsive biomimetic nanopores which are created with DNA nanotechnology. The nanopores switch between open and closed states, whereby specific binding of DNA and protein molecules as stimuli locks the pores in the open state. Furthermore, the physical stimulus of high transmembrane voltage switches the pores into a closed state. In addition, the pore diameters are larger and more tunable than those of natural templates. These multi-stimuli-responsive and mechanically actuated nanopores mimic several aspects of complex biological channels yet offer easier control over pore size, shape and stimulus response. The designer pores are expected to be applied in biosensing and synthetic biology.

Bio-Inspired Subnanofluidics: Advanced Fabrication and Functionalization.

Biological ion channels can realize high-speed and high-selective ion transport through the protein filter with the sub-1-nanometer channel. Inspired by biological ion channels, various kinds of artificial subnanopores, subnanochannels, and subnanoslits with improved ion selectivity and permeability are recently developed for efficient separation, energy conversion, and biosensing. This review article discusses the advanced fabrication and functionalization methods for constructing subnanofluidic pores, channels, tubes, and slits, which have shown great potential for various applications. Novel fabrication methods for producing subnanofluidics, including top-down techniques such as electron beam etching, ion irradiation, and electrochemical etching, as well as bottom-up approaches starting from advanced microporous frameworks, microporous polymers, lipid bilayer embedded subnanochannels, and stacked 2D materials are well summarized. Meanwhile, the functionalization methods of subnanochannels are discussed based on the introduction of functional groups, which are classified into direct synthesis, covalent bond modifications, and functional molecule fillings. These methods have enabled the construction of subnanochannels with precise control of structure, size, and functionality. The current progress, challenges, and future directions in the field of subnanofluidic are also discussed.