Graphite‐Based Bio‐Mimetic Nanopores for Protein Sequencing and Beyond

Protein sequencing using nanopores represents the next frontier in bio‐analytics. However, linearizing unfolded proteins and controlling their translocation speed through solid‐state nanopores pose significant challenges in protein sequencing. In order to address these issues, this work proposes a b...

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Veröffentlicht in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2025-01, Vol.21 (2), p.e2407647-n/a
Hauptverfasser: Das, Chandan K., Fyta, Maria
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Sprache:eng
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Zusammenfassung:Protein sequencing using nanopores represents the next frontier in bio‐analytics. However, linearizing unfolded proteins and controlling their translocation speed through solid‐state nanopores pose significant challenges in protein sequencing. In order to address these issues, this work proposes a biomimetic graphite‐based nanopore construction. These nanopores feature a nanometer‐sized pore with a constriction zone, mimicking the structure of the α‐hemolysin protein pore. Our all‐atom Molecular Dynamics simulations demonstrate the high practical potential of these nanopores by revealing how their charge state renders them complete ion‐selective and generates an electro‐osmotic flow. This study shows that this nanopore construction can detect peptides at the single amino acid level by analyzing the ionic current traces generated as peptides traverse the nanopore. The novelty of the proposed nanopore lies in its ability to modulate the hydrodynamic drag induced by electro‐osmotic flow, relative to the electro‐phoretic force. This investigation reveals that tuning these forces helps to linearize translocating peptides and extend the residence time of individual amino acids at the constriction zone of the pore. This significantly enhances the detection and sequencing efficiency of the pore. Furthermore, the high relevance of the proposed nanopores is underscored for seawater desalination through electrodialysis and extends to ion separation under salinity gradients. A graphite‐based nanopore, inspired from α‐hemolysin, enables protein sequencing and single amino acid detection by leveraging charge‐driven ion selectivity and electro‐osmotic flow. This tunable nanopore design also offers promising applications in seawater desalination and renewable energy generation through salinity gradient exploitation.
ISSN:1613-6810
1613-6829
1613-6829
DOI:10.1002/smll.202407647