Ion Permeability Research Articles

Shutters-Inspired metal ions coordination hydrogel Strain/Pressure sensor for joint behavior evaluation and flatfeet correction

The metal ions coordination hydrogels (MI-HG) that polymer gels serve as flexible substrates and metal ions as conductive media have emerged as flexible electronic sensor materials. Nevertheless, fabricating MI-HG by a traditional soaking method is difficult to guarantee the good permeation of metal ions, manifesting as the “core–shell” structure of MI-HG, which undoubtedly reduces their mechanical property, conductivity, and sensitivity. Inspired by the shutter opening and closing regulation mechanism, a strategy that completely opening the backbone layers of polymer gels facilitates metal ions permeation thus improving the whole performance of MI-HG, especially the mechanical property is proposed. Herein, poly(vinyl alcohol)(poly(acrylic acid)-polyacrylamide) (PVA(PAA-PAM)) is used as the typical polymer hydrogel (HG), trivalent aluminum ion (Al3+) as the metal salt, and N,N'-methylenebisacrylamide (MBAA) as the important regulation ‘rod’, fabricating a series of aluminum coordination hydrogels (Al-HGx%). The results indicate that the mechanical performances of Al-HG2% are significantly improved. For example, the toughness of Al-HG2% reaches 996.12 KJ/m3, approximately three times that of the Al-HG0% sample (354.45 KJ/m3). The combination of structural characterization as well as finite element analysis, the mechanism for the enhanced mechanical performances based on shutter’s completely open effect is elucidated, the product of which (Al-HG2%) has potential application in flexible strain/pressure sensor for joint behavior evaluation and flatfeet correction.

Structural basis for human Cav3.2 inhibition by selective antagonists

The Cav3.2 subtype of T-type calcium channels has been targeted for developing analgesics and anti-epileptics for its role in pain and epilepsy. Here we present the cryo-EM structures of Cav3.2 alone and in complex with four T-type calcium channel selective antagonists with overall resolutions ranging from 2.8 Å to 3.2 Å. The four compounds display two binding poses. ACT-709478 and TTA-A2 both place their cyclopropylphenyl-containing ends in the central cavity to directly obstruct ion flow, meanwhile extending their polar tails into the IV-I fenestration. TTA-P2 and ML218 project their 3,5-dichlorobenzamide groups into the II-III fenestration and place their hydrophobic tails in the cavity to impede ion permeation. The fenestration-penetrating mode immediately affords an explanation for the state-dependent activities of these antagonists. Structure-guided mutational analysis identifies several key residues that determine the T-type preference of these drugs. The structures also suggest the role of an endogenous lipid in stabilizing drug binding in the central cavity.

Nanochannel Stability of Chemically Converted Graphene Oxide Membranes.

Chemically converted graphene oxide laminate membranes, which exhibit stable interlayered nanochannels in aqueous environments, are receiving increasing attention owing to their potential for selective water and ion permeation. However, how the molecular properties of conversion agents influence the stabilization of nanochannels and how effectively nanochannels are stabilized have rarely been studied. In this study, mono-, di-, and tri-saccharide molecules of glucose (Glu), maltose (Glu2), and maltotriose (Glu3) are utilized, respectively, to chemically modify graphene oxide (GO). The aim is to create nanochannels with different levels of stability and investigate how these functional conversion agents affect the separation performance. The effects of the property differences between different conversion agents on nanochannel stabilization are demonstrated. An agent with efficient chemical reduction of GO and limited intercalation in the resulting nanochannel ensures satisfactory nanochannel stability during desalination. The stabilized membrane nanochannel exhibits a permeance of 0.69 L m-2 h-1 bar-1 and excellent Na2SO4 rejection of 96.42%. Furthermore, this optimized membrane nanochannel demonstrates enhanced stability under varying external conditions compared to the original GO. This study provides useful information for the design of chemical conversion agents for GO nanochannel stabilization and the development of nanochannel membranes for precise separation.

Direct conversion of monopotassium L-aspartate by electrodialysis metathesis: Stack resistance, co-ion transport, and concentration polarization

The conventional method of synthesizing high-value amino salt from amino acid ammonium involves several steps including acidification, precipitation, and separation. This process not only consumes acids and bases but also generates a substantial amount of wastewater. In this study, monoammonium L-aspartate was directly converted to monopotassium L-aspartate (Asp-K) using electrodialysis metathesis (EDM). To achieve this, K2SO4 was chosen as the optimum potassium salt to supply K+ due to its relatively lower co-transport rate with SO42− ions and lower stack resistance. Additionally, the membrane type was optimized as CIS/AIS membranes due to their low stack resistance, high ion permeability for the transport of Asp− ions, and low concentration polarization. The process resulted in high-purity Asp-K (99.8 %) and low energy consumption (0.14 kWh/kg Asp-K). These results indicate that the EDM process is a promising method for converting amino salts with high purity.

Performance of concrete produced with alkali-activated artificial aggregates

The excessive use of natural aggregates raises mining activity. Further, it leads to environmental damage, which can be reduced using artificial aggregates produced from waste powdered materials. This study discussed the production process of alkali-activated artificial coarse aggregates and how their use affects the behavior of concrete. The different concrete mixtures were designed by replacing natural aggregates with artificial ones at different percentages. Various tests were conducted to determine concrete’s fresh, hardened, permeability, and microstructural characteristics. The result showed that concrete incorporated with artificial aggregates can achieve higher workability and lower density than natural aggregate concrete. The mechanical strengths were slightly decreased as the percentage addition of artificial aggregates in a mix increased. However, adding up to 50% showed comparable results to natural aggregate concrete. The water permeability and chloride ion penetration were within the standard limits for all the mixes. The scanning electron micrographs showed a solid and compact ITZ between the phases. XRD pattern revealed that the addition of artificial aggregates had not changed the mineralogical composition of the concrete; the formation of hydrated products helps concrete obtain strength. The study concluded that artificial aggregates could effectively replace natural coarse aggregate in producing structural concrete with many advantages.

Mechanical activation opens a lipid-lined pore in OSCA ion channels.

OSCA/TMEM63 channels are the largest known family of mechanosensitive channels1-3, playing critical roles in plant4-7 and mammalian8,9 mechanotransduction. Here we determined 44 cryogenic electron microscopy structures of OSCA/TMEM63 channels in different environments to investigate the molecular basis of OSCA/TMEM63 channel mechanosensitivity. In nanodiscs, we mimicked increased membrane tension and observed a dilated pore with membrane access in one of the OSCA1.2 subunits. In liposomes, we captured the fully open structure of OSCA1.2 in the inside-in orientation, in which the pore shows a large lateral opening to the membrane. Unusually for ion channels, structural, functional and computational evidence supports the existence of a 'proteo-lipidic pore' in which lipids act as a wall of the ion permeation pathway. In the less tension-sensitive homologue OSCA3.1, we identified an 'interlocking' lipid tightly bound in the central cleft, keeping the channel closed. Mutation of the lipid-coordinating residues induced OSCA3.1 activation, revealing a conserved open conformation of OSCA channels. Our structures provide a global picture of the OSCA channel gating cycle, uncover the importance of bound lipids and show that each subunit can open independently. This expands both our understanding of channel-mediated mechanotransduction and channel pore formation, with important mechanistic implications for the TMEM16 and TMC protein families.

Structural insights into ion selectivity and transport mechanisms of Oryza sativa HKT2;1 and HKT2;2/1 transporters.

Plant high-affinity K+ transporters (HKTs) play a pivotal role in maintaining the balance of Na+ and K+ ions in plants, thereby influencing plant growth under K+-depleted conditions and enhancing tolerance to salinity stress. Here we report the cryo-electron microscopy structures of Oryza sativa HKT2;1 and HKT2;2/1 at overall resolutions of 2.5 Å and 2.3 Å, respectively. Both transporters adopt a dimeric assembly, with each protomer enclosing an ion permeation pathway. Comparison between the selectivity filters of the two transporters reveals the critical roles of Ser88/Gly88 and Val243/Gly243 in determining ion selectivity. A constriction site along the ion permeation pathway is identified, consisting of Glu114, Asn273, Pro392, Pro393, Arg525, Lys517 and the carboxy-terminal Trp530 from the neighbouring protomer. The linker between domains II and III adopts a stable loop structure oriented towards the constriction site, potentially participating in the gating process. Electrophysiological recordings, yeast complementation assays and molecular dynamics simulations corroborate the functional importance of these structural features. Our findings provide crucial insights into the ion selectivity and transport mechanisms of plant HKTs, offering valuable structural templates for developing new salinity-tolerant cultivars and strategies to increase crop yields.

TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.

Excitotoxicity and the concurrent loss of inhibition are well-defined mechanisms driving acute elevation in excitatory/inhibitory (E/I) balance and neuronal cell death following an ischemic insult to the brain. Despite the high prevalence of long-term disability in survivors of global cerebral ischemia (GCI) as a consequence of cardiac arrest, it remains unclear whether E/I imbalance persists beyond the acute phase and negatively affects functional recovery. We previously demonstrated sustained impairment of long-term potentiation (LTP) in hippocampal CA1 neurons correlating with deficits in learning and memory tasks in a murine model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Here, we use CA/CPR and an in vitro ischemia model to elucidate mechanisms by which E/I imbalance contributes to ongoing hippocampal dysfunction in male mice. We reveal increased postsynaptic GABAA receptor (GABAAR) clustering and function in the CA1 region of the hippocampus that reduces the E/I ratio. Importantly, reduced GABAAR clustering observed in the first 24 h rebounds to an elevation of GABAergic clustering by 3 d postischemia. This increase in GABAergic inhibition required activation of the Ca2+-permeable ion channel transient receptor potential melastatin-2 (TRPM2), previously implicated in persistent LTP and memory deficits following CA/CPR. Furthermore, we find Ca2+-signaling, likely downstream of TRPM2 activation, upregulates Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, thereby driving the elevation of postsynaptic inhibitory function. Thus, we propose a novel mechanism by which inhibitory synaptic strength is upregulated in the context of ischemia and identify TRPM2 and CaMKII as potential pharmacological targets to restore perturbed synaptic plasticity and ameliorate cognitive function.

Honeybee CaV4 has distinct permeation, inactivation, and pharmacology from homologous NaV channels.

DSC1, a Drosophila channel with sequence similarity to the voltage-gated sodium channel (NaV), was identified over 20 years ago. This channel was suspected to function as a non-specific cation channel with the ability to facilitate the permeation of calcium ions (Ca2+). A honeybee channel homologous to DSC1 was recently cloned and shown to exhibit strict selectivity for Ca2+, while excluding sodium ions (Na+), thus defining a new family of Ca2+ channels, known as CaV4. In this study, we characterize CaV4, showing that it exhibits an unprecedented type of inactivation, which depends on both an IFM motif and on the permeating divalent cation, like NaV and CaV1 channels, respectively. CaV4 displays a specific pharmacology with an unusual response to the alkaloid veratrine. It also possesses an inactivation mechanism that uses the same structural domains as NaV but permeates Ca2+ ions instead. This distinctive feature may provide valuable insights into how voltage- and calcium-dependent modulation of voltage-gated Ca2+ and Na+ channels occur under conditions involving local changes in intracellular calcium concentrations. Our study underscores the unique profile of CaV4 and defines this channel as a novel class of voltage-gated Ca2+ channels.

Growing ZIF-L seeds in graphene oxide interlayers towards synthesizing efficient cation sieving membranes

Designing and synthesizing membranes with fast and selective cation transport remains extremely challenging. Herein, ZGO membranes are conceived via a two-dimensional zeolitic imidazolate framework (ZIF-L) in situ grown on graphene oxide (GO), with ZIF-L as an interlayer that increases both vertical interlayer spacing and lateral tortuous path spacing of GO, thus improving the stability, selectivity, and ion permeation of the ZGO lamellar membrane. Structural analyses reveal that GO surfaces with abundant oxygen functional groups favored the formation of ZIF-L with 316 crystal planes and offered a high ion-accessible surface area. More importantly, the ZGO membrane delivers an excellent K+ permeability of 86.9 mmol m−2 h−1 and K+/Mg2+ selectivity up to 266, outperforming state-of-the-art GO-based membranes. Furthermore, molecular simulations confirm that the hydrogen bonding between hydrated cations and polar functional groups of ZGO membranes substantially restricted the dynamical transport of bivalent cation, and thus led to excellent cation selectivity. These results open a pathway to developing membranes for fast and highly selective ion separations in the future.

Research on chloride ion permeability resistance of concretes bonded with CFRP sheets under dry-wet cycles

Considering the widespread application of carbon fibre-reinforced polymer (CFRP) as a protective material for reinforced concrete (RC) structures, this study focuses on the ability of CFRP laminates with different numbers of layers bonded to the concrete surface to reduce the ingress of chloride ions. Variations in the free chloride concentration distribution in concrete before and after CFRP bonding were explored systematically. Nonlinear fitting was applied to the experimental data to establish a calculation model for the diffusion of free chloride ions in concrete with CFRP bonded to the surface, which was subsequently validated. Based on the proposed model, the reduction in the surface chloride concentration of concrete after bonding different numbers of CFRP layers was quantified as the reduction value. Moreover, recommendations for the durable design of RC structures bonded with CFRP in wet-dry cyclic environments are provided. The results indicate that the surface chloride concentration in concrete increases continuously with increasing wet-dry cycles, eventually reaching a steady state. Compared with the concrete specimens without CFRP bonding, the bonding of one, two, or three layers of CFRP led to reductions in the stable surface chloride concentration of concrete by 70.8%, 82.6%, and 84.9%, respectively. And no obvious convection zone was observed in the concrete after CFRP bonding. The validation results of the proposed calculation model demonstrated its high accuracy, making it suitable for durable design and service life prediction.

Graphene oxide-based nanofluidic system for power generation from salinity difference

In converting a salinity difference to the electrical power by using an ion-selective membrane, achieving a high-power density necessitates both a high ion permeability and ion selectivity of the membrane. However, meeting these two requirements often leads to the conflicting tradeoff in the membrane properties. In this study, we introduce a new mechanistic approach to meeting both requirements by combining an ultra-thin (<100 nm thickness) graphene oxide-based membrane for a high permeability with an asymmetric access area for a high ion selectivity, forming a new type of ionic-diode nanofluidic system. With a graphene oxide/silk fibroin composite membrane, a large power density of 2kW/m2 is achieved with 32% conversion efficiency under a 1000-fold salt concentration ratio. This approach can be utilized to overcome the low power density limitation with any ultra-thin membranes, and thereby it will provide a new route to utilize blue energy in a reliable and efficient way.

Approaching Tryptophan-Derived Polynorbornene Fluorescent Chemosensors: Synthesis, Characterization, and Sensing Ability for Biomedical Applications as Biomarkers for Detecting Fe2+ Ions.

We present a novel group of tryptophan (Trp)-based fluorescent polymeric probes synthesized via ring-opening metathesis polymerization (ROMP) of Trp-derived norbornene monomers. These probes, in mono- and disubstituted forms, incorporate amide and ester anchoring groups. The quantity of Trp substituents did not affect fluorescence selectivity but influenced quenching percentage. Poly-diamide-Trp, Poly-monoamide-Trp, Poly-diester-Trp, and Poly-monoester-Trp probes displayed selective detection of Fe2+ and Fe3+ ions with fluorescence on-off characteristics. Poly-diamide-Trp and Poly-monoamide-Trp exhibited a limit of detection (LOD) for Fe2+ and Fe3+ ions of 0.86-11.32 μM, while Poly-diester-Trp and Poly-monoester-Trp showed higher LODs (21.8-108.7 μM). These probes exhibited high selectivity over Fe2+, a crucial metal ion in the body known for its redox properties causing oxidative stress and cell damage. Cell cytotoxicity tests in various cell types confirmed biocompatibility. Additionally, Poly-diamide-Trp displayed excellent cell permeability and iron ion detection in EA.hy926 cells, suggesting potential for bioimaging and clinical applications.

Disposal of solid waste as building materials: A study on the mechanical and durability performance of concrete composed of gold tailings

The purpose of this study is to explore the possibility of gold tailings as an alternative to natural river sand for preparing concrete, to solve the problems of rapid increase in gold tailings and insufficient natural river sand stock. Additionally, gold tailings upgraded by centrifugal separation are compared with untreated gold tailings. The performances and modification mechanisms of gold tailings on the mechanical strength and durability performance of concrete were investigated. The results demonstrate that concrete composed of gold tailings exhibits commendable mechanical and durability properties, with the optimal replacement level of natural river sand being 30%. Replacing river sand with gold tailings enhances the compressive and split tensile strengths of concrete, reduces water absorption, and improves its resistance to freeze-thaw cycles and chloride ion permeability, primarily owing to the pozzolanic activity and filling effect of the gold tailings. The upgrading of gold tailings not only changed altered the particle size but also changed the active SiO2 and Al2O3 content, thus, further enhancing the mechanical and durability of concrete. The study establishes that utilizing gold tailings in construction can serve as a viable substitute for river sand, thereby mitigating potential environmental repercussions associated with gold tailings. The findings hold promise for diminishing the reliance on river sand, thereby markedly enhancing resource sustainability.

Modified Bacteria Incorporated Geopolymer - A Qualitative Approach for an Eco-friendly, Energy-efficient and Self-healing Construction Material

Cement production consumes huge energy and creates environmental pollution. Cracks present in the cement-based concretes, deteriorate the structural longevity and requires costly repair. An eco-friendly and energy-efficient geopolymeric material is developed by incorporating modified bacterium cells, assuming that the developed material will be a cement-alternatives in construction industries in near future. Transformed Bacillus subtilis cells is incorporated to the alkali-activated fly ash only (100%) for making the geo-polymeric material. The mortar samples prepared by geopolymeric material are cured under various conditions to achieve the best possible energy-efficient curing process. Simulated cracks on mortars are developed by applying 50% (half) of predetermined breaking load for studying the self-healing phenomenon. Artificial cracks on mortars are created by introducing steel bar for studying crack-repairing activity. Mechanical strengths (compressive, tensile and flexural), water permeability, sulfate and chloride resistant activities along with the crack-repairing and the self-healing efficacy of the samples are characterized. Higher mechanical strengths and better longevity in terms of decreased water and chloride ions permeability and increased sulfate resistant activity are noted in the bacterium amended mortars. Ambient temperature modified heat curing process reveals the best possible energy-efficient curing condition. Images and micro-structures analyses show that several new phases (e.g., silicate, mullite, albite and alite etc.) are developed within the bacteria-amended mortars. Eco-friendliness of the bacterium is confirmed by toxicity study against rats models and human cell lines. We hypothesize that the developed geo-polymeric material is a suitable cement alternative in construction industries as well as an eco-friendly and energy efficient material.

Effect of electron beam irradiation on hole structure of cellulose acetate membrane

Cellulose acetate (CA) is one of the most popular biomaterials used for filtration membranes in water treatment.In this study, the CA membranes immersing in water were irradiated by electron beam, and the hole structure of CA membranes at different irradiation doses was investigated. The SEM pictures show the combination of micro-meter sized pores in CA membrane during the irradiation process. The electrochemical impedance spectroscopy(EIS) results reveal the membrane resistance decreases with the irradiation dose, which implies easier ion permeation. The positron annihilation lifetime measurement (PAL) results indicate the mean free-volume hole size becomes smaller with increasing irradiation dose. The above results demonstrate that electron beam irradiation would lead to chain scission of CA, and then the formation of new pores and pores combination, which provides more channels for ion permeation. FTIR results suggest stronger hydrogen bonding in CA after the irradiation in water. The differential scanning calorimetry (DSC)results indicate that the crystallinity has been enhanced with the irradiation dose up to 10 kGy and reduces in the range from 10 kGy to 80 kGy. The results could provide the clues explaining the performance deterioration of CA membrane during treating radioactive waste water.

Effect of ionic association on the pressure-driven Li+/Mg2+ permselective transport through nanochannels

It is extremely significant to develop lithium recovery technology due to the growing consumption of the lithium in the past few years. Membrane separation offers a green process for lithium recovery, however, there are still some debates on its mechanism. Ionic association is a common behavior among the cation–anion interaction in the aqueous solution, which is believed to take effect on the ionic permeation through the available membranes. In this work, a series of MD simulations were performed to unravel the effect of ionic association on the Li+/Mg2+ permselective transport through one-dimensional nanochannels, which were modelled for mimicking the channels with the interested sizes of the commonly-used membranes rather than any specific membranes. Two types of structural evolutions (i.e. dehydration and disassociation) were found during the penetration of the ionic associations into the nanochannels, the ionic associations significantly impede the ionic transmembrane permeation. The electrostatic affinity of the cations determines the structure of the ionic associations. As a result, the divalent Mg2+ ions lead to a preferred formation of hyper-associations, which makes the Mg2+ associations have to enter into the nanochannel via disassociation. While it is relatively easy for the Li+ associations to squeeze into the confinement via disassociation or dehydration, and even some free Li+ ions could penetrate into the nanochannels. However, the coexistence of the Li+ and Mg2+ ions greatly deteriorates the preferential permeation to Li+ ions due to the enhance ionic association, which thus greatly reduces the Li+/Mg2+ permselectivity. Therefore, it is of significant importance to disorganize the ionic association structures of the Li+ and Mg2+ ions in order to achieve a precise size-sieving capacity of nanochannels for efficient Li+/Mg2+ separation. This work not only helps understand the effect of association on membrane-based Li+/Mg2+ separation, but also promotes the development of high-performance membranes for Li+/Mg2+ separation.

Optimizing ionic conductivity and ion selectivity in zinc-polyiodide flow batteries with composite polyamide-porous separators

Owing to their superior theoretical energy capacity, zinc-polyiodide flow batteries (ZIFBs) are well-known energy storage devices. The practicality of ZIFBs depends on the development of cost-effective separators that can demonstrate both excellent ionic conductivity and selective ion permeability. Herein, an economical polymer blend comprising poly (ether sulfone) (PES) and sulfonated poly (ether ether ketone) (sPEEK) is fabricated via a phase inversion technique. Due to the formation of a sponge-like structure, the porous substrate indicates high ionic conductivity. Furthermore, the selected porous substrate is coated with a thin-film polyamide, synthesized from m-phenylenediamine (MPD) and 1,3,5-benzene tricarbonyl trichloride (TMC) via interfacial polymerization (IP). This polyamide layer can efficiently mitigate the undesired migration of triiodide ions, while maintaining high ionic conductivity. This innovative approach yields a composite separator having a deftly tunable structure. Using such a separator, ZIFBs can operate stably with high coulombic efficiency (CE) of 91 % over 100 cycles at a current density of 10 mAh cm−2. Overall, this study explores the trade-off between ionic conductivity and ion permeability. It is seen that by adjusting their morphology, the physical characteristics of the composite separators can be improved, ensuring stable and efficient operation of ZIFBs.

Chloride ion permeability of concrete containing recycled composite powder from building demolition waste

Buildings in the marine environment are vulnerable to chloride ion erosion, which threatens the service life of concrete structures. To facilitate the application of concrete containing construction demolition waste in the marine environment, recycled composite powder concrete (RCPC) was prepared using recycled composite powder as cement substitute. The chloride ion permeability of RCPC was evaluated by chloride ion diffusion test and rapid chloride ion migration test (RCM). The chloride ion permeability of RCPC continued to enhance with growing content of recycled composite powder. During the immersion age, the surface chloride ion content of the samples containing recycled composite powder increased by an average of 18.3–65.3% over the control group, with a corresponding average increase in chloride ion diffusion coefficients ranging from 17.0% to 31.5%. The chloride ion migration coefficients in the RCM test raised by 9.5–24.7%. A series of microscopic tests such as nuclear magnetic resonance (NMR), X-ray diffraction (XRD) and scanning electron microscope-energy dispersive spectrometer (SEM-EDS) suggested that the total porosity increased by 11.9–29.5% with the addition of recycled composite powder. The chloride ion diffusion coefficients exhibited a linear increase with growing total porosity and porosity of capillary pores, whereas an exponential increase with the porosity of transitional pores. The poor reactivity of the recycled composite powder resulted in a looser microstructure and weakened chloride binding capacity, and these factors boosted chloride ion transport. A chloride ion diffusion model of RCPC considering the time dependence of chloride ion transport was developed, and the reliability of the model was verified by experimental data.

Knock-out of dipeptidase CN2 in human proximal tubular cells disrupts dipeptide and amino acid homeostasis and para- and transcellular solute transport.

Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase-2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. We therefore hypothesized, that CN2 has a key metabolic role, impacting proximal tubular transport function. A knockout of the CN2 gene (CNDP2-KO) was generated in human proximal tubule cells and characterized by metabolomics, RNA-seq analysis, paracellular permeability analysis and ion transport. CNDP2-KO in human proximal tubule cells resulted in the accumulation of cellular dipeptides, reduction of amino acids and imbalance of related metabolic pathways, and of energy supply. RNA-seq analyses indicated altered protein metabolism and ion transport. Detailed functional studies demonstrated lower CNDP2-KO cell viability and proliferation, and altered ion and macromolecule transport via trans- and paracellular pathways. Regulatory and transport protein abundance was disturbed, either as a consequence of the metabolic imbalance or the resulting functional disequilibrium. CN2 function has a major impact on intracellular amino acid and dipeptide metabolism and is essential for key metabolic and regulatory functions of proximal tubular cells. These findings deserve invivo analysis of the relevance of CN2 for nephron function and regulation of body homeostasis.