Biomimetic Nanochannels Research Articles

Regulation of transmembrane current through modulation of biomimetic lipid membrane composition.

Ion transport through biological channels is influenced not only by the structural properties of the channels themselves but also by the composition of the phospholipid membrane, which acts as a scaffold for these nanochannels. Drawing inspiration from how lipid membrane composition modulates ion currents, as seen in the activation of the K+ channel in Streptomyces A (KcsA) by anionic lipids, we propose a biomimetic nanochannel system that integrates DNA nanotechnology with two-dimensional graphene oxide (GO) nanosheets. By modifying the length of the multibranched DNA nanowires generated through the hybridization chain reaction (HCR) and varying the concentration of the linker strands that integrate these DNA nanowire structures with the GO membrane, the composition of the membrane can be effectively adjusted, consequently impacting ion transport. This method provides a strategy for developing devices with highly efficient and tunable ion transport, suitable for applications in mass transport, environmental protection, biomimetic channels, and biosensors.

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.

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.

TRPM4-Inspired Polymeric Nanochannels with Preferential Cation Transport for High-Efficiency Salinity-Gradient Energy Conversion.

Biological ion channels exhibit switchable cation transport with ultrahigh selectivity for efficient energy conversion, such as Ca2+-activated TRPM4 channels tuned by cation-π interactions, but achieving an analogous highly selective function is challenging in artificial nanochannels. Here, we design a TRPM4-inspired cation-selective nanochannel (CN) assembled by two poly(ether sulfone)s, respectively, with sulfonate acid and indole moieties, which act as cation-selective activators to manage Na+/Cl- selectivity via ionic and cation-π interactions. The cation selectivity of CNs can be activated by Na+, and thereby the Na+ transference number significantly improves from 0.720 to 0.982 (Na+/Cl- selectivity ratio from 2.6 to 54.6) under a 50-fold salinity gradient, surpassing the K+ transference number (0.886) and Li+ transference number (0.900). The TRPM4-inspired nanochannel membrane enabled a maximum output power density of 5.7 W m-2 for salinity-gradient power harvesting. Moreover, a record energy conversion efficiency of up to 46.5% is provided, superior to most nanochannel membranes (below 30%). This work proposes a novel strategy to biomimetic nanochannels for highly selective cation transport and high-efficiency salinity-gradient energy conversion.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

DNA-Peptide Interaction-Modulated Charge Reversal in Biomimetic Nanochannels for Simple and Efficient Detection of Histone Deacetylases.

Protein acetylation, a fundamental post-translational modification, plays a critical role in the regulation of gene expression and cellular processes. Monitoring histone deacetylases (HDACs) is important for understanding epigenetic dynamics and advancing the early diagnosis of malignancies. Here, we leverage the dynamic characteristics of DNA-peptide interactions in biomimetic nanochannels to develop a HDAC detection method. In specific, the catalysis of peptide deacetylation by HDACs triggers alterations in the charge states of the nanochannel surface to accommodate DNA molecules. Then, the interaction between DNA and peptides shifts the nanochannel surface charge from positive to negative, leading to a reversal of the ion current rectification (ICR). By calculation of the ICR ratio, quantitative detection of HDACs can be efficiently achieved using the nanochannel-based method in an enzyme-free and label-free manner. Our experimental results demonstrate that HDACs can be detected by using this method within a concentration range of 0.5-500 nM. The innate simplicity and efficiency of this strategy may render it a valuable tool for advancing both fundamental research and clinical applications in the realm of epigenetics and personalized medicine.

Rectifying artificial nanochannels with multiple interconvertible permeability states

Transmembrane channels play a vital role in regulating the permeation process, and have inspired recent development of biomimetic channels. Herein, we report a class of artificial biomimetic nanochannels based on DNAzyme-functionalized glass nanopipettes to realize delicate control of channel permeability, whereby the surface wettability and charge can be tuned by metal ions and DNAzyme-substrates, allowing reversible conversion between different permeability states. We demonstrate that the nanochannels can be reversibly switched between four different permeability states showing distinct permeability to various functional molecules. By embedding the artificial nanochannels into the plasma membrane of single living cells, we achieve selective transport of dye molecules across the cell membrane. Finally, we report on the advanced functions including gene silencing of miR-21 in single cancer cells and selective transport of Ca2+ into single PC-12 cells. In this work, we provide a versatile tool for the design of rectifying artificial nanochannels with on-demand functions.

Nano-Confined Effect and Heterojunction Promoted Exciton Separation for Light-Boosted Osmotic Energy Conversion.

The osmotic energy conversion properties of biomimetic light-stimulated nanochannels have aroused great interest. However, the power output performance is limited by the low light-induced current and energy conversion efficiency. Here, nanochannel arrays with simultaneous modification of ZnO and di-tetrabutylammonium cis-bis(isothiocyanato)bis(2,20-bipyridyl-4,40-dicarboxylato) ruthenium (II) (N719) onto anodic aluminum oxide (AAO) to combine the nano-confined effect and heterojunction is designed, which demonstrate rectified ion transport behavior due to the asymmetric composition, structure and charge. High cation selectivity and ion flux contribute to the high power density of ≈7.33Wm-2 by mixing artificial seawater and river water. Under light irradiation, heterojunction promoted the production and separation of exciton, enhanced cation selectivity, and improved the utilization efficiency of osmotic energy, providing a remarkable power density of ≈18.49Wm-2 with an increase of 252% and total energy conversion efficiency of 30.43%. The work opens new insights into the biomimetic nanochannels for high-performance energy conversion.

Single-Cell Caspase-3 Measurement Using a Biomimetic Nanochannel.

Direct single-cell caspase-3 (Casp-3) analysis has remained challenging. A study of single-cell Casp-3 could contribute to revealing the fundamental pathogenic mechanisms in Casp-3-associated diseases. Here, a biomimetic nanochannel capable of single-cell sampling and ionic detection of intracellular Casp-3 is devised, which is established upon the installment of target-specific organic molecules (luc-DEVD) within the orifice of a glass nanopipette. The specific cleavage of luc-DEVD by Casp-3 could induce changes of inner-surface chemical groups and charge properties, thus altering the ionic response of the biomimetic nanochannel for direct Casp-3 detection. The practical applicability of this biomimetic nanochannel is confirmed by probing intracellular Casp-3 fluctuation upon drug stimulation and quantifying the Casp-3 evolution during induced apoptosis. This work realizes ionic single-cell Casp-3 analysis and provides a different perspective for single-cell protein analysis.

Biomimetic construction of smart nanochannels in covalent organic framework membranes for efficient ion separation

Smart nanochannels can regulate ion transport behavior by external stimulus and display precise ion selectivity in biological membrane systems, but constructing artificial membranes with responsive and tunable channel remains a severe challenge. Herein, smart covalent organic framework (COF) membranes decorated with photo-responsive azobenzene derivatives (COF-Azo) were fabricated by a biomimetic nanochannel modulation (BNM) strategy, endowing membranes with charged and switchable sub-nanochannels. Under different wavelength of light, the smart COF-Azo membranes simultaneously exhibited outstanding mono/monovalent and mono/divalent ion selectivity (K+/Li+ ideal selectivity of 17.9 and Li+/Mg2+ ideal selectivity of 24.9) via closing and opening channels. The conversion of effective pore size at angstrom level is realized by photoisomerization of azobenzene. After several photoswitch cycles, the smart membranes still maintained K+/Li+ selectivity of 6.1 and Li+/Mg2+ selectivity of 20.7 in mixed salt solution, exhibiting great potentials in lithium extraction. This work may blaze a trail in constructing photo-responsive nanochannel membranes for energy-efficient ion separation.

Pure Covalent-Organic Framework Membrane as a Label-Free Biomimetic Nanochannel for Sensitive and Selective Sensing of Chiral Flavor Substances.

Chiral flavor substances play an important role in the human perception of different tastes. Here, we report a pure covalent-organic framework (COF) membrane nanochannel in combination with a chiral gold nanoparticles (AuNPs) selector for sensing chiral flavor substances. The pure COF membrane with a proper pore size is selected as the nanochannel, while l-cysteine-modified AuNPs (l-Cys-AuNPs) are used as the chiral selector. l-Cys-AuNPs show stronger binding to the S-enantiomer than the R-enantiomer, causing current reduction to different degrees for the R- and S-enantiomer to achieve chiral sensing due to the synergistic effect of the size exclusion of the COF nanochannel and the chiral selectivity of l-Cys-AuNPs. The developed COF membrane nanochannel sensing platform not only allows an easy balance of the permeability and selectivity, which is difficult to achieve in traditional polymer membrane nanochannel sensors, but also exhibits better chiral performance than commercial artificial anodic aluminum oxide (AAO) nanochannel sensors. The developed nanochannel sensor is successfully applied for sensing flavor enantiomers such as limonene, propanediol, methylbutyric acid, and butanol with the enantiomer excess values of 55.2% (propanediol) and 72.4% (limonene) and the low detection limits of 36 (limonene) and 71 (propanediol) ng L-1. This study provides a new idea for the construction of nanochannel platforms based on the COF for sensitive and selective chiral sensing.

Engineering ATP activated reversible nanochannel for gating of ion transport

Adenosine triphosphate (ATP) is an important purine molecule. It widely exists in cells and is closely related to a variety of significant physiological and pathological processes, such as energy metabolism, respiratory regulation, inflammation, and so forth. In vivo, ATP not only provides energy for organisms at the molecular level but also activates intracellular ion channels and regulates signaling pathways. Therefore, it is of great significance to construct ATP-responsive nanochannels for understanding complex biological processes. In this work, we designed and fabricated multi-amino conjugated rhodamine B (NH2-RhB) functionalized artificial nanochannels, which exhibited high performance for ATP response with current and fluorescence dual signals. Significantly, owing to the non-covalent bonding of NH2-RhB and ATP, the system performed reversible properties for regulating ion transport and behaved as an ionic gate that can flexibly switch between the "on" and "off" state under the condition of ATP and pH. The platform showed high selectivity for ATP and the detection limit can be as low as 48.2 fM. Moreover, finite-element theoretical simulation was employed to reveal the mechanism of ATP-activated nanochannel regulating ion flux. It proved that the surface charge density of the NH2-RhB functionalized nanochannels can be regulated by dealing with ATP and pH. This work shows promising applications of biomimetic nanochannel with gating properties and offers prospects for the development of biosensing, nanodevice, and nanofluidic logic gates.

Switchable biomimetic nanochannels for on-demand SO2 detection by light-controlled photochromism

In contrast to the conventional passive reaction to analytes, here, we create a proof-of-concept nanochannel system capable of on-demand recognition of the target to achieve an unbiased response. Inspired by light-activatable biological channelrhodopsin-2, photochromic spiropyran/anodic aluminium oxide nanochannel sensors are constructed to realize a light-controlled inert/active-switchable response to SO2 by ionic transport behaviour. We find that light can finely regulate the reactivity of the nanochannels for the on-demand detection of SO2. Pristine spiropyran/anodic aluminium oxide nanochannels are not reactive to SO2. After ultraviolet irradiation of the nanochannels, spiropyran isomerizes to merocyanine with a carbon‒carbon double bond nucleophilic site, which can react with SO2 to generate a new hydrophilic adduct. Benefiting from increasing asymmetric wettability, the proposed device exhibits a robust photoactivated detection performance in SO2 detection in the range from 10 nM to 1 mM achieved by monitoring the rectified current.

Ultra-low concentrations of detection for fluoride and trivalent chromium ions by multiple biomimetic nanochannels in a PET membrane

The development of a detection method for fluoride and chromium (III) ions using a PET membrane with multiple biomimetic nanochannels is descibed. An asymmetric chemical etching technique was used to create conical nanochannels with a PET (polyethylene terephthalate) nuclear track membrane. SEM images showed that the pore diameter of the tip and base sides of the nanochannel were ∼40 nm and ∼180 nm, respectively. The compounds (4-aminophenyl) boronic acid (APBA) and 5-amino-2-nitrobenzoic acid (ANBA), with a specific recognition for F− and Cr3+ respectively, were modified by a conventional method with EDC and NHS. The current-voltage (I–V) curves of the modified PET membranes in response to the target ions at different concentrations were measured with a picoammeter. Excellent linear relationships between the current value of the I–V curve at −2 V and the concentration of Cr3+ and F− were established to obtain standard detection curves for Cr3+ and F−. From these relationships unknown concentrations of Cr3+ and F− can be quantitatively detected, and the results showed that the detection limits of Cr3+ and F− were as low as 4.10 nM and 0.46 nM, respectively. The performance of the novel method was compared to conventional ICP-MS analysis by the determination of Cr3+ in tap water and samples of the Jing Mi diversion canal, and good agreement was found between the two methods. The accuracy and reliability of the method has demonstrated its potential applicability to a wide range of other ionic contaminants.

Biomimetic nanochannels for molybdate transport: application to sensitive electrochemical immunoassay for HER2

A nanochannel-based electrochemical immunoassay was developed for the detection of human epidermal growth factor receptor 2 (HER2), with molybdate as the reporter to explore the interaction occurring into the nanochannels. The presence of target increased steric hindrance of the antibody-functionalized nanochannels, thereby hindering the transport of molybdate. And the reporter could be monitored by working electrode modified with hydroxyapatite nanoparticles, based on the formation of the redox-active molybdophosphate. As a result, peak current obtained at ca. - 0.28V in square wave voltammograms could be applied to quantitative determination of HER2. The electrochemical signal increased linearly with the logarithm of the concentration of HER2 in a broad dynamic range of 0.1pg∙mL-1 to 10ng∙mL-1 with a detection limit of 0.05pg∙mL-1. The reliability of this immunoassay was validated by a recovery range of 99.5% to 111.7% for the detection of three different levels of HER2 in human serum samples. Integrating with multiple bionanochannels, this immunoassay is expected to provide a versatile approach for quantitative detection of various biomarkers in related disease diagnosis and therapy.

Ion transport behavior in a vertically-oriented asymmetric Ti3C2Tx nanochannel membrane

Exceptional ion release and storage ability of biological ion channels are regarded as a prerequisite for various life activities. Constructing biomimetic nanochannels to modulate selective ion transport has received enormous attention. Herein, a study on ion transport behavior in a vertically-oriented three-sectional Ti3C2Tx membrane with asymmetric charge distribution was presented. The surface charge polarity of Ti3C2Tx nanosheet was changed from negativity to positivity by successfully grafting the silane molecules onto the surface. The heterogenous Ti3C2Tx nanochannel membrane consisting of three different charged sections was prepared to build up the nanofluidic device. The diode-like ion transport property was observed for the heterogenous membrane, and the maximum ion current rectification ratio reached approximately 32. The numerical simulation based on the Poisson-Nernst-Planck (PNP) equations indicated that the directional ion diffusion was attributed to the accumulation and depletion of ions in the nanochannels under different potential biases. Moreover, the application potential of desalination and ion storage of the heterogenous membrane was assessed. Our work paves the way for the design of heterogenous nanochannels for controllable ion transport and introduces a new perspective for ion sieving, energy conversion, and sensing applications.

A novel biosensor based on AAO nanochannels modified with ZnS nanostructure for sensitive detection of tetracycline

• A confined self-assembly system based on AAO/ZnS for the detection of tetracycline is fabricated. • The current change ratios of tetracycline detection in the presence of different concentration are calculated. • The system is valid for the detection of tetracycline with an excellent sensitivity. Herein, a confined self-assembly system based on AAO/ZnS for the detection of tetracycline is fabricated in this article. According to the optimized experimental results, when the aperture of AAO, the reaction time, and the reaction voltage are 80–100 nm, 30 min, and 1.5 V, respectively, the best assembly system is obtained. In addition, the detection sensitivity of the system for tetracycline is investigated and the experimental results show that this system is effective and sensitive for the detection of tetracycline. This work not only proposes a new idea for combining nanomaterials and biomimetic nanochannels, but also exhibits great potential in improving the sensitivity of detecting biomolecules.

Light-responsive nanochannels based on the supramolecular host-guest system.

The light-responsive nanochannel of rhodopsin gained wider research interest from its crucial roles in light-induced biological functions, such as visual signal transduction and energy conversion, though its poor stability and susceptibility to inactivation in vitro have limited its exploration. However, the fabrication of artificial nanochannels with the properties of physical stability, controllable structure, and easy functional modification becomes a biomimetic system to study the stimulus-responsive gating properties. Typically, light-responsive molecules of azobenzene (Azo), retinal, and spiropyran were introduced into nanochannels as photo-switches, which can change the inner surface wettability of nanochannels under the influence of light; this ultimately results in the photoresponsive nature of biomimetic nanochannels. Furthermore, the fine-tuning of their stimulus-responsive properties can be achieved through the introduction of host–guest systems generally combined with a non-covalent bond, and the assembling process is reversible. These host–guest systems have been introduced into the nanochannels to form different functions. Based on the host–guest system of light-responsive reversible interaction, it can not only change the internal surface properties of the nanochannel and control the recognition and transmission behaviors but also realize the controlled release of a specific host or guest molecules in the nanochannel. At present, macrocyclic host molecules have been introduced into nanochannels including pillararenes, cyclodextrin (CD), and metal–organic frameworks (MOFs). They are introduced into the nanochannel through chemical modification or host–guest assemble methods. Based on the changes in the light-responsive structure of azobenzene, spiropyran, retinal, and others with macrocycle host molecules, the surface charge and hydrophilic and hydrophobic properties of the nanochannel were changed to regulate the ionic and molecular transport. In this study, the development of photoresponsive host and guest-assembled nanochannel systems from design to application is reviewed, and the research prospects and problems of this photo-responsive nanochannel membrane are presented.

Highly efficient monovalent ion transport enabled by ionic crosslinking‐induced nanochannels

AbstractCharge‐governed ion transport is of significant importance to industrial development, and advanced membrane materials with fast and selective ionic transport are essential components. In cell membranes, ionic transport is mainly determined by the charge‐governed protein channels, representing an architecture with functional differentiation. Inspired by this, a novel class of membranes was developed by ionically crosslinking sulfonated (poly[ether ether ketone]) and quaternized poly(2,6‐dimethyl‐1,4‐phenylene oxide) to construct the cationic conductive biomimetic nanochannels. Ionic crosslinking was tailored to realize nanophase separation and efficient ion transport mainly based on surface chemistry without altering the scaffold feature of polymeric pore channels. The best‐performing ionic crosslinking membrane exhibited a high ionic permeation (2.23 mol·m−2·h−1 for K+) and high cationic selectivity (7.91 for K+/Mg2+), which were comparable with the commercial monovalent cation permselective CIMS membrane, owing to the negligent surface resistance toward monovalent cations but strong positively charged repulsion against divalent cations.

Proton diffusion and hydrolysis enzymatic reaction in 100 nm scale biomimetic nanochannels.

Liquids in 10-100 nm spaces are expected to play an important role in biological systems. However, the liquid properties and their influence on biological activity have been obscured due to the difficulty in nanoscale measurements, either in vivo or in vitro. In this study, an in vitro analytical platform for biological systems is established. The nanochannels were modified with lipid bilayers, thereby serving as a model for biological confinement, e.g., the intercellular or intracellular space. As a representative property, the proton diffusion coefficient was measured by a nanofluidic circuit using fluorescein as a pH probe. It was verified that proton conduction was enhanced for channel widths less than 330 nm. A proton-related enzymatic reaction, the hydrolysis reaction, was also investigated, and a large confinement effect was observed.