Biological Ion Channels Research Articles

Biocompatible Acellular Dermal Matrix-Based Neuromorphic Device with Ultralow Voltage, Ion Channel Emulation, and Synaptic Forgetting Visualization Computation.

Neuromorphic bioelectronics aim to integrate electronics with biological systems yet encounter challenges in biocompatibility, operating voltages, power consumption, and stability. This study presents biocompatible neuromorphic devices fabricated from acellular dermal matrix (ADM) derived from porcine dermis using low-temperature supercritical CO2 extraction. The ADM preserves the natural scaffold structure of collagen and minimizes immunogenicity by eliminating cells, fats, and noncollagenous impurities, ensuring excellent biocompatibility. The ADM-based devices emulate biological ion channels with biphasic membrane current modulation, exhibiting temperature dependency and pH sensitivity. It operates at an ultralow voltage of 1 mV and demonstrates reliable synaptic modulation exceeding 4 × 104 endurance cycles. The activation voltage can be theoretically as low as 59 μV, comparable to brainwave signals with a power of merely 7 aJ/event. Furthermore, a brain-like forgetting visualization algorithm is developed, leveraging the synaptic forgetting plasticity of ADM-based devices to achieve complex computing tasks in a highly energy-efficient manner. Neuromorphic devices based on ADM not only hold potential in implantable biointerfaces due to their exceptional biocompatibility, ultralow voltage, and power but also provide a feasible way for energy-efficient computing paradigms through a synergistic hardware-software approach.

Biology, function and structure of the calcium homeostasis modulator family.

Calcium homeostasis modulators (CALHMs) are the most recently discovered members of the large-pore channel family. They mediate the conductance of ions and larger molecules, such as ATP, and play critical roles in pathways related to Alzheimer's disease, neuroinflammation, neuromodulation, taste perception and innate immune responses. Since the inaugural report on CALHM1 in 2008, significant breakthroughs have revealed their biological roles, ion and ATP channel functions, and structures, positioning the field for further advancements. In this review, we discuss the overall progress and recent developments in understanding the biological roles, functions and molecular structures of CALHM proteins.

Sub-nanoporous polyimide membrane with selective and fast K+ transport

Biological ion channels have excellent monovalent ion separation performance, and it is of great significance to develop artificial membrane materials with monovalent ion selectivity based on their mechanism. The latent-track method is a new technology to prepare sub-nanometer channels on polymer membranes by swift heavy ion irradiation. This method has been widely applied in the study of mono/divalent ion separation membranes, but its application in monovalent ion separation membranes still needs to be explored. In this work, polyimide (PI) film was irradiated by swift heavy ion, then water rinsed, and the sub-nanoporous PI membrane with effective channel size in the range of 0.30 and 0.66 nm was fabricated, then its electrical and transport properties were studied. Due to the smaller hydrated diameter and lower hydration energy of K+, the membrane exhibited good selectivity for K+. The selectivity ratio of K+/Li+ is 3.4–3.9, and the maximum K+ flux can reach 0.44 mol m−2 h−1 at 55℃. The sub-nanoporous PI membranes are expected to be applied in salt lake lithium extraction, fine processing of potassium and lithium, and other relevant scenarios.

Modular Plasmonic Nanopore for Opto‐Thermal Gating

AbstractSolid‐state nanopore gating inspired by biological ion channels is gaining increasing traction due to a large range of applications in biosensing and drug delivery. Integration of stimuli‐responsive molecules such as poly(N‐isopropylacrylamide) (PNIPAM) inside nanopores can enable temperature‐dependent gating, which so far has only been demonstrated using external heaters. In this work, plasmonic resonators are combined inside the nanopore architecture with PNIPAM to enable optical gating of individual or multiple nanopores with micrometer resolution and a switching speed of a few milliseconds by thermo‐plasmonics effects. A temperature change of 40 kelvin per millisecond is achieved and demonstrates the efficacy of this method using nanopore ionic conductivity measurements that enable selective activation of individual nanopores in an array. Moreover, the selective gating of specific nanopores in an array can set distinct ionic conductance levels: low, medium, and high (i.e., “0,” “1,” and “2”), which can be exploited for logical gating with optical signal control. Such selective optical gating in nanopore arrays marks a breakthrough in nanofluidics, as it paves the way toward smart devices that offer multifunctional applications including biosensing, targeted drug delivery, and fluidic mixing.

Electric Field Mediated Unclogging of Angstrom-Scale Channels.

Angstrom-scale fluidic channels offer immense potential for applications in areas such as desalination, molecular sieving, biomolecular sequencing, and dialysis. Inspired by biological ion channels, nano- and angstrom (Å)-scale channels are fabricated that mimic these molecular or atomic-scale dimensions. At the Å-scale, these channels exhibit unique phenomena, including selective ion transport, osmotic energy generation, fast water and gas flows, and neuromorphic ion memory. However, practical utilization of Å-scale channels is often hindered by contamination, which can clog these nanochannels. In this context, a promising technique is introduced here for unclogging 2D channels, particularly those with sub-nanometre dimensions (≈6.8 Å). The voltage-cycling method emerges as an efficient and reliable solution for this challenge. The electric field effectively dislodges contaminants from the clogged Å-scale channels, facilitating ion and molecular transport. This study provides practical guidelines for reviving clogged nano- and Å-scale channels, thereby enhancing their applicability in various ion and molecular transport applications.

High-speed Ta2O5-based threshold switching memristor for LIF neurons

Due to their high similarity to biological ion channels, low power consumption, small footprint, and the fact that they do not require reset circuits, threshold switching memristors have been intensively studied for simulating neurons in neuromorphic chips. Switching speed is one of the key challenges which limit the application of threshold switching memristors in chips. In this study, Ta2O5 threshold switching memristors with high switching speeds were prepared by doping with silver. The results show that 14 wt. % Ag doped Ta2O5 threshold switching memristors exhibit excellent bi-directional threshold switching performance, featuring fast switching speeds (<20 ns, <18 ns), low leakage currents (<10 pA), and high switching ratio (>107). According to the field nucleation theory, the rapid switching speed can be attributed to the low nucleation energy (0.26 eV) of silver within the Ta2O5 matrix, which is achieved by incorporating 14 wt. % Ag during the doping process. Based on Pspice, a LIF (leaky integrate-and-fire) neuron based on the silver nanoparticles doped Ta2O5 threshold switching memristors is built, and its firing function has been simulated. The results show that the LIF neuron with a short switching time is able to excite pulse spiking with high frequencies. These results demonstrated that the silver nanoparticles doped Ta2O5-based threshold switching memristors hold significant potential for constructing high-speed artificial neural networks.

Bioinspired recognition in metal-organic frameworks enabling precise sieving separation of fluorinated propylene and propane mixtures

The separation of fluorinated propane/propylene mixtures remains a major challenge in the electronics industry. Inspired by biological ion channels with negatively charged inner walls that allow selective transport of cations, we presented a series of formic acid-based metal-organic frameworks (MFA) featuring biomimetic multi-hydrogen confined cavities. These MFA materials, especially the cobalt formate (CoFA), exhibit specific recognition of hexafluoropropylene (C3F6) while facilitating size exclusion of perfluoropropane (C3F8). The dual-functional adsorbent offers multiple binding sites to realize intelligent selective recognition of C3F6, as supported by theoretical calculations and in situ spectroscopic experiments. Mixed-gas breakthrough experiments validate the capability of CoFA to produce high-purity (>5 N) C3F8 in a single step. Importantly, the stability and cost-effective scalable synthesis of CoFA underscore its extraordinary potential for industrial C3F6/C3F8 separations. This bioinspired molecular recognition approach opens new avenues for the efficient purification of fluorinated electronic specialty gases.

Tuning Nanochannel Microenvironments of a Thermoresponsive MXene Membrane for Mixed Molecule Gradient Separation.

Drawing inspiration from dynamic biological ion channels, researchers have developed various artificial membranes featuring responsive nanochannels. Typically, these membranes modify mass transport behaviors by manipulating the responsive layer on the inner surfaces of the intrinsic layer. In this study, we build two-dimensional lamellar membranes composed of titanium carbide MXene and poly(N-isopropylacrylamide), endowed with dual-level regulatable nanochannels, achieved through adjustments of nanochannel microenvironments. The size of these two-dimensional nanochannels can be altered by both the thermoresponsive polymer layer and the intrinsic MXene layer that could undergo spontaneous oxidation. The multilevel regulation strategy substantially enhances the molecular selectivity of MXene separation membranes, which is further applied for precise gradient separation toward multiple molecules. This advancement showcases the versatility and transformative capabilities of responsive nanochannel technology, setting the stage for innovative developments in diverse fields.

Biomimetic Channels Design in Metal-Organic Framework Enabling Highly Lithium-Ion Conduction for Lithium-Metal Batteries.

Solid-state electrolytes (SSEs) based on metal-organic frameworks (MOFs) are an ideal material for constructing high-performance lithium metal batteries (LMBs). However, the low ion conductivity and poor interface contact (especially at low temperatures) still seriously hinder its further application. Herein, inspired by the Na+/K+ conduction in biology systems, a series (NH2, OH, NH-(CH2)3-SO3H)-modified MIL-53-X as SSEs is reported. These functional groups are similar to anions suspended in biological ion channels, partially repelling anions while allowing cations to be effectively transported through pore channels. Subsequently, MIL-53-X with hierarchical pore structure (H-MIL-53-X) is obtained by introducing lauric acid as a regulator, and then the effects of structural design and morphology control on its performance are explored. The conductivity of H-MIL-53-NH-SO3Li with multi-level pore structure and modified by sulfonic acid groups reached 2.2×10-3Scm-1 at 25°C, lithium-ion transference number of 0.78. Besides, the H-MIL-53-NH-SO3Li still has an excellent conductivity of 10-4Scm-1 at -40°C. Additionally, LiFePO4/Li batteries equipped with H-MIL-53-NH-SO3Li SSEs could operate stably for over 200 cycles at 0.1C. The strategy of combining structural and morphological design of MOFs with biomimetic ion channels opens new avenues for the design of high-performance SSEs.

Mechanically activated and deactivated ion transport across nanopores with heterogeneous surface charge distributions

To mimic the intricate and adaptive functionalities of biological ion channels, electrohydrodynamic ion transport has been studied extensively, albeit mostly, across uniformly charged nanochannels. Here, we analyze the ion transport under coupled electric field and pressure across heterogeneously charged nanopores with oppositely charged sections on their lateral surface. We only consider such pores with symmetric hourglass-like and cylindrical shapes to focus on the effects of the non-uniform surface charge distribution. Finite-element simulations of a continuum model demonstrate that a pressure applied in either direction of the pore-axis equally suppresses or amplifies the ionic conductance, depending on the electric field polarity, by distorting the quasi-static distribution of ions in the pore. The resulting anomalous mechanical deactivation and activation of ionic current under opposite voltage biases exhibit the functional modularity of our setup, while their intensities are highly tunable, substantially greater than those of analogous behaviors in other nanochannels, and fundamentally correlated to ionic current rectification (ICR) in our pores. A detailed study of ICR subsequently reveals its counterintuitive non-monotonous variations, in the pores, with the magnitude of applied voltage and the pore length, that can help optimize their diode-like behavior. We further illustrate that while the hourglass-shaped nanopores yield the more efficient mechanical suppressors of ion transport, their cylindrical analogs are the superior rectifiers and mechanical amplifiers of ion conduction. Therefore, this article provides a blueprint for the strategic design of nanofluidic circuits to attain a robust, modular, and tunable control of ion transport under external electrical and mechanical stimuli.

Modular Customized Biomimetic Nanofluidic Diode for Tunable Asymmetric Ion Transport.

Artificial ion diodes, inspired by biological ion channels, have made significant contributions to the fields of physics, chemistry, and biology. However, constructing asymmetric sub-nanofluidic membranes that simultaneously meet the requirements of easy fabrication, high ion transport efficiency, and tunable ion transport remains a challenge. Here, a direct and flexible in situ staged host-guest self-assembly strategy is employed to fabricate ion diode membranes capable of achieving zonal regulation. Coupling the interfacial polymerization process with a host-guest assembly strategy, it is possible to easily manipulate the type, order, thickness, and charge density of each module by introducing two oppositely charged modules in stages. This method enables the tuning of ion transport behavior over a wide range salinity, as well as responsive to varying pH levels. To verify the potential of controllable diode membranes for application, two ion diode membranes with different ion selectivity and high charge density are coupled in a reverse electrodialysis device. This resulted in an output power density of 63.7W m-2 at 50-fold NaCl concentration gradient, which is 12 times higher than commercial standards. This approach shows potential for expanding the variety of materials that are appropriate for microelectronic power generation devices, desalination, and biosensing.

Precise control of transmembrane current via regulating bionic lipid membrane composition.

The transport of ions through biological ion channels is regulated not only by their structural characteristics but also by the composition of the phospholipid membrane, which serves as a carrier for nanochannels. Inspired by the modulation of ion currents by lipid membrane composition, exemplified by the activation of the K+ channel of Streptomyces A by anionic lipids, we present a biomimetic nanochannel system based on combining DNA nanotechnology with two-dimensional graphene oxide (GO) nanosheets. By designing multibranched DNA nanowires, we assemble programmable DNA scaffold networks (DSNs) on the GO surface to precisely control membrane composition. Modulating the DSN layers from one to five enhances DNA composition, yielding a maximum 12-fold enhancement in ion current, primarily due to charge effects. Incorporating DNAzymes facilitates reversible modulation of membrane composition, enabling cyclic conversion of ion current. This approach offers a pathway for creating devices with highly efficient, tunable ion transport, applicable in diverse fields like mass transport, environmental protection, biomimetic channels, and biosensors.

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

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

A physical derivation of high-flux ion transport in biological channel via quantum ion coherence

Biological ion channels usually conduct the high-flux transport of 107 ~ 108 ions·s−1; however, the underlying mechanism is still lacking. Here, by applying the KcsA potassium channel as a typical example, and performing multitimescale molecular dynamics simulations, we demonstrate that there is coherence of the K+ ions confined in biological channels, which determines transport. The coherent oscillation state of confined K+ ions with a nanosecond-level lifetime in the channel dominates each transport event, serving as the physical basis for the high flux of ~108 ions∙s−1. The coherent transfer of confined K+ ions only takes several picoseconds and has no perturbation effect on the ion coherence, acting as the directional key of transport. Such ion coherence is allowed by quantum mechanics. An increase in the coherence can significantly enhance the ion conductance. These findings provide a potential explanation from the perspective of coherence for the high-flux ion transport with ultralow energy consumption of biological channels.

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.

A Bioinspired Membrane with Ultrahigh Li+/Na+ and Li+/K+ Separations Enables Direct Lithium Extraction from Brine.

Membranes with precise Li+/Na+ and Li+/K+ separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic-scale distinctions among these monovalent cations. Herein, inspired by the strict size-sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long-range ordered ion channels that exclusively permeate naked Li+ but block Na+ and K+. This naked-Li+-sieving behavior not only enables unprecedented Li+/Na+ and Li+/K+ selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state-of-the-art membranes by at least two orders of magnitude, but also demonstrates impressive Li+/Mg2+ and Li+/Ca2+ separation capabilities. Moreover, this bioinspired membranehas to be utilized for creating a one-step lithium extraction strategy from natural brines rich in Na+, K+, and Mg2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion-sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction.

A highly-selective biomimetic potassium channel.

Reproducing the outstanding selectivity achieved by biological ion channels in artificial channel systems can revolutionize applications ranging from membrane filtration to single-molecule sensing technologies, but achieving this goal remains a challenge. Herein, inspired by the selectivity filter structure of the KcsA potassium channel, we propose a design of biomimetic potassium nanochannels by functionalizing the wall of carbon nanotubes with an array of arranged carbonyl oxygen atoms. Our extensive molecular dynamics simulations show that the biomimetic nanochannel exhibits a high K+ permeation rate along with a high K+/Na+ selectivity ratio. The free energy calculations suggest that the low Na+ permeability is the result of the higher energy barrier for Na+ than K+ at the channel entrance and ion binding sites. In addition, reducing the number of ion binding sites leads to an increase in the permeation rate but a decrease in selectivity. These findings not only hold promise for the design of high-performance membranes but also help understand the mechanism of selective ion transport in biological ion channels.

High-efficiency dysprosium-ion extraction enabled by a biomimetic nanofluidic channel

Biological ion channels exhibit high selectivity and permeability of ions because of their asymmetrical pore structures and surface chemistries. Here, we demonstrate a biomimetic nanofluidic channel (BNC) with an asymmetrical structure and glycyl-L-proline (GLP) -functionalization for ultrafast, selective, and unidirectional Dy3+ extraction over other lanthanide (Ln3+) ions with very similar electronic configurations. The selective extraction mainly depends on the amplified chemical affinity differences between the Ln3+ ions and GLPs in nanoconfinement. In particular, the conductivities of Ln3+ ions across the BNC even reach up to two orders of magnitude higher than in a bulk solution, and a high Dy3+/Nd3+ selectivity of approximately 60 could be achieved. The designed BNC can effectively extract Dy3+ ions with ultralow concentrations and thereby purify Nd3+ ions to an ultimate content of 99.8 wt.%, which contribute to the recycling of rare earth resources and environmental protection. Theoretical simulations reveal that the BNC preferentially binds to Dy3+ ion due to its highest affinity among Ln3+ ions in nanoconfinement, which attributes to the coupling of ion radius and coordination matching. These findings suggest that BNC-based ion selectivity system provides alternative routes to achieving highly efficient lanthanide separation.

Spontaneous Transition between Multiple Conductance States and Rectifying Behaviors in an Artificial Single‐Molecule Funnel

It has long been an aspirational goal to create artificial channel structures that replicate the feat achieved by ion channel proteins. Biological ion channels occasionally demonstrate multiple conductance states (known as subconductance), remaining a challenging property to achieve in artificial channel molecules. We report a funnel‐shaped single‐molecule channel constructed by an electron‐deficient macrocycle and two electron‐deficient aromatic imide arms. Planar lipid bilayer measurements reveal distinct current recordings, including a closed state, two conducting states, and spontaneous transitions between the three states, resembling the events seen in biological ion channels. The transitions result from conformational changes induced by chloride transport in the channel molecule. Both opening states show a non‐linear and rectifying I‐V relationship, indicating voltage‐dependent transport due to the asymmetrical channel structure. This work could enhance our understanding of ion permeation and channel opening mechanism.

Exploring the influence of pore shape on conductance and permeation

There are increasing numbers of ion channel structures featuring heteromeric subunit assembly, exemplified by synaptic α1βB glycine and α4β2 nicotinic receptors. These structures exhibit inherent pore asymmetry, but the relevance of this to function is unknown. Furthermore, molecular dynamics simulations performed on symmetrical homomeric channels often lead to thermal distortion whereby conformations of the resulting ensemble are also asymmetrical. When functionally annotating ion channels, researchers often rely on minimal constrictions determined via radius-profile calculations performed with computer programs, such as HOLE or CHAP, coupled with an assessment of pore hydrophobicity. However, such tools typically employ spherical probe particles, limiting their ability to accurately capture pore asymmetry. Here, we introduce an algorithm that employs ellipsoidal probe particles, enabling a more comprehensive representation of the pore geometry. Our analysis reveals that the use of nonspherical ellipsoids for pore characterization provides a more accurate and easily interpretable depiction of conductance. To quantify the implications of pore asymmetry on conductance, we systematically investigated carbon nanotubes with varying degrees of pore asymmetry as model systems. The conductance through these channels shows surprising effects that would otherwise not be predicted with spherical probes. The results have broad implications not only for the functional annotation of biological ion channels but also for the design of synthetic channel systems for use in areas such as water filtration. Furthermore, we make use of the more accurate characterization of channel pores to refine a physical conductance model to obtain a heuristic estimate for single-channel conductance. The code is freely available, obtainable as pip-installable python package and provided as a web service.