Nanopore Discriminates Watson–Crick and Hoogsteen Hydrogen Bonds in Multiple DNA Contexts

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Watson-Crick and Hoogsteen hydrogen bonds aid the formation of highly ordered structures in genomic DNA that dynamically govern genetic modes such as gene regulation replication. Hence, measuring distinguishing these two types different contexts are essential for understanding architectures. However, due to their transient nature minimal structure differences at sub-nanometer scale, differentiating from is difficult. Relying on nanopore technology, we successfully discriminated multiple presence epigenetic modification, changes structures, proton strength environment. Our results indicate show susceptibilities physicochemical characteristics matter stabilizing bonds. This work provides insight into features nanoscale may benefit profiling complex architectures by subtle structural changes.

Language: Английский

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Nanopore approaches for single-molecule temporal omics: promises and challenges

Nature Methods, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

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Aerolysin Nanopore Electrochemistry

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ConspectusIons are the crucial signaling components for living organisms. In cells, their transportation across pore-forming membrane proteins is vital regulating physiological functions, such as generating ionic current signals in response to target molecule recognition. This ion transport affected by confined interactions and local environments within protein pore. Therefore, can efficiently transduce characteristics of each into ion-transport-mediated with high sensitivity. Inspired nature, various pores have been developed high-throughput label-free nanopore sensors single-molecule detection, enabling rapid accurate readouts. particular, aerolysin, a key virulence factor Aeromonas hydrophila, exhibits sensitivity fingerprints detecting subtle differences sequence, conformation, structure DNA, proteins, polypeptides, oligosaccharides, other molecules. Aerolysin features cap that approximately 14 nm wide on cis side central pore about 10 long minimum diameter around 1 nm. Its lumen, 11 charged rings at two entrances neutral amino acids between, facilitates dwelling single analyte characteristic enables rich between well-defined residues analyte. As result, signal offers unique molecular fingerprint, extending beyond traditional volume exclusion model sensing. 2006, aerolysin was first reported discriminate conformational peptides, opening door rapidly growing field electrochemistry. Over years, mutant nanopores emerged, associated advanced instrumentation data analysis algorithms, simultaneous identification over 30 targets number still increasing. electrochemistry particular allows time-resolved qualitative quantitative ranging from DNA sequencing, proteomics, enzyme kinetics, reactions potential clinical diagnostics. Especially, feasibility dynamic would revolutionize omics studies level, paving way promising temporal omics. Despite success this approach so far, it remains challenging understand how correlate distinguishable signatures. Recent attempts added correction terms account variations mobility caused Account, we revisit origin blockade induced molecules inside nanopore. We highlight contributions noncovalent sensing ability through corrected conductance model. Account then describes design interaction networks nanopore, including electrostatic, hydrophobic, hydrogen-bonding, cation−π, ion–charged acid interactions, ultrasensitive biomolecular quantification. Finally, provide an outlook further understanding network improving manipulating fine-tuning toward broad range practical applications.

Language: Английский

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Transmembrane voltage-gated nanopores controlled by electrically tunable in-pore chemistry

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 5, 2025

Gating is a fundamental process in ion channels configured to open and close response specific stimuli such as voltage across cell membranes thereby enabling the excitability of neurons. Here we report on voltage-gated solid-state nanopores by electrically tunable chemical reactions. We demonstrate repetitive precipitation dissolution metal phosphates pore through manipulations cation flow transmembrane voltage. Under negative voltages, precipitates grow reduce ionic current occluding nanopore, while inverting polarity dissolves phosphate compounds reopening flux. Reversible actuation these physicochemical processes creates nanofluidic diode rectification ratio exceeding 40000. The dynamic nature in-pore reactions also facilitates memristor sub-nanowatt power consumption. Leveraging degrees freedom, present method may be useful for creating iontronic circuits characteristics toward neuromorphic systems. Ion electrical stimuli, playing critical role cellular signaling homeostasis. Here, authors show similar gating functionality nanopores, achieved control chemistry.

Language: Английский

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Dynamic chemical modifications and chemical interventions of G protein-coupled receptor

Scientia Sinica Chimica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Obtaining Narrow Distributions of Single-Molecule Peptide Signals Enables Sensitive Peptide Discrimination with α-Hemolysin Nanopores

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Biological nanopore technology has emerged as a promising tool for analyzing peptides and post-translational modifications at the single-molecule level. However, broader application is currently limited by partial separation of low-throughput, mainly due to nonuniform peptide signals detected nanopores. Narrowing signal distribution crucial improving nanopore's sensing ability but remains bottleneck. Here, we demonstrate that capturing with electrophoretic force against electroosmotic flow can provoke more uniform blockades in α-hemolysin By using buffers 2 M KCl pH 3.8, obtain most signals, which may be correlated shape, linearization, actual dwelling position peptides. Five acetylation phosphorylation, including isomeric peptides, readily separated from each other. The citrullination replacement arginine β-hydroxybutyrylation modification another sequence are also discriminated mixture. A series different compositions induced when they were analyzed our method. Our work presents an efficient approach optimize analysis

Language: Английский

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Enzyme-less discrimination of chiral amino acids with femtoampere-level precision by proton-driven anthrax nanopore

Published: March 18, 2025

The precise detection of amino acids and the identification their chirality are paramount importance in protein sequencing, design druggable molecules, diagnosis diseases based on damage. However, this remains an exceptionally challenging task. Herein, we developed a novel nanopore system anthrax protective antigen, proton-driven transmembrane channel, for discrimination 20 proteinogenic chiral enantiomers. By employing pH-asymmetric ionic liquids instead traditional salt conditions, effectively resolved intrinsic limitations (i.e., current fluctuation, low signal-to-noise ratio, gating phenomenon) wild-type sensing activity. optimized demonstrated exceptional sensitivity differentiating as well levorotary dextrorotary enantiomers at femtoampere precision (< 100 fA). mechanism various through signals can be attributed to inhomogeneous intermolecular interactions—such electrostatic forces, π-πinteractions, hydrogen bonding—between inner surface nanopore. These interactions, conjunction with either electrophoretic forces or electroosmotic flow, collectively enable differentiation distinct acid types. Notably, nanopore-based method eliminates need enzymes, chemical reactions, machine learning algorithms. Instead, it relies solely electrolyte direct interpretation signatures achieve discrimination. This study provides idea architecture that offers ultrahigh resolution, wide dynamic range enantioselectivity, specificity, thereby having implications sequencing making available refined analytical tool revealing properties molecules diverse biological contexts.

Language: Английский

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Regulation of Protein Transport in Functionalized PET Nanopores

The Journal of Physical Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Facilitated translocation is a critical mechanism for transporting substances in biological systems, where molecular and ionic species move across the membrane with help of specific transmembrane protein ion channels. In this work, we systematically examined transport three poly(ethylene terephthalate) (PET) nanopores modified different types surface functions (hydroxyl, phenyl, amine). We found that event signature as well kinetics thermodynamics movement PET nanopore varied significantly change function pore. addition to electrophoretic effect, other factors such diffusion, electro-osmotic selectivity channel, affinity strength between functional group also play significant roles transport. Although properly functionalized individual can be used stochastic elements rapid differentiation characterization, enhanced resolution accuracy could accomplished by employing an array having inner groups characterize proteins based on their collective responses. Given important living organisms applications biomarkers early disease diagnosis prognosis, pattern-recognition solid-state nanopore-sensing strategy detection characterization developed work may find useful various fields.

Language: Английский

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Single molecular profile of proteins sensing by nanopore technology

Talanta, Journal Year: 2025, Volume and Issue: unknown, P. 128040 - 128040

Published: March 1, 2025

Language: Английский

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Nanopore sensing of protein and peptide conformation for point-of-care applications

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 4, 2025

Abstract The global population’s aging and growth will likely result in an increase chronic aging-related diseases. Early diagnosis could improve the medical care quality of life. Many diseases are linked to misfolding or conformational changes biomarker peptides proteins, which affect their function binding properties. Current clinical methods struggle detect quantify these changes. Therefore, there is a need for sensitive sensors that can low-concentration analytes biofluids. Nanopore electrical detection has shown potential sensing subtle protein peptide conformation This technique single molecules label-free while distinguishing shape physicochemical property Its proven sensitivity makes nanopore technology promising ultra-sensitive, personalized point-of-care devices. We focus on capability detecting quantifying modifications enantiomers proteins discuss this as solution future societal health challenges.

Language: Английский

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