Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers

The transport of DNA polymers through nanoscale pores is central to many biological processes, from bacterial gene exchange to viral infection. In single-molecule nanopore sensing, the detection of nucleic acid and protein analytes relies on the passage of a long biopolymer through a nanoscale apert...

Full description

Saved in:
Bibliographic Details
Main Authors: Fei Zheng, Antonio Suma, Christopher Maffeo, Kaikai Chen, Mohammed Alawami, Jingjie Sha, Aleksei Aksimentiev, Cristian Micheletti, Ulrich F. Keyser
Format: Article
Language:English
Published: American Physical Society 2025-08-01
Series:Physical Review X
Online Access:http://doi.org/10.1103/spyg-kl86
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849390761718579200
author Fei Zheng
Antonio Suma
Christopher Maffeo
Kaikai Chen
Mohammed Alawami
Jingjie Sha
Aleksei Aksimentiev
Cristian Micheletti
Ulrich F. Keyser
author_facet Fei Zheng
Antonio Suma
Christopher Maffeo
Kaikai Chen
Mohammed Alawami
Jingjie Sha
Aleksei Aksimentiev
Cristian Micheletti
Ulrich F. Keyser
author_sort Fei Zheng
collection DOAJ
description The transport of DNA polymers through nanoscale pores is central to many biological processes, from bacterial gene exchange to viral infection. In single-molecule nanopore sensing, the detection of nucleic acid and protein analytes relies on the passage of a long biopolymer through a nanoscale aperture. Understanding the dynamics of polymer translocation through nanopores, especially the relation between ionic current signal and polymer conformations, is thus essential for the successful identification of targets. Here, by analyzing ionic current traces of dsDNA translocation, we reveal that features up to now uniquely associated with knots are instead different structural motifs: plectonemes. By combining experiments and simulations, we demonstrate that such plectonemes form because of the solvent flow that induces rotation of the helical DNA fragment in the nanopore, causing torsion propagation outwards from the pore. Molecular dynamic simulations reveal that plectoneme nucleation is dominated by the applied torque, while the translocation time and size of the plectonemes depend on the coupling of torque and pulling force, a mechanism that might also be relevant for in vivo DNA organization. Experiments with nicked DNA constructs show that the number of plectonemes depends on the rotational constraints of the translocating molecules. Thus, our work introduces plectonemes as essential structural features that must be considered for accurate analysis of dsDNA polymers in the nanopore.
format Article
id doaj-art-35588dc4ee9f42acb4dd2a18cd707641
institution Kabale University
issn 2160-3308
language English
publishDate 2025-08-01
publisher American Physical Society
record_format Article
series Physical Review X
spelling doaj-art-35588dc4ee9f42acb4dd2a18cd7076412025-08-20T03:41:21ZengAmerican Physical SocietyPhysical Review X2160-33082025-08-0115303104110.1103/spyg-kl86Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA PolymersFei ZhengAntonio SumaChristopher MaffeoKaikai ChenMohammed AlawamiJingjie ShaAleksei AksimentievCristian MichelettiUlrich F. KeyserThe transport of DNA polymers through nanoscale pores is central to many biological processes, from bacterial gene exchange to viral infection. In single-molecule nanopore sensing, the detection of nucleic acid and protein analytes relies on the passage of a long biopolymer through a nanoscale aperture. Understanding the dynamics of polymer translocation through nanopores, especially the relation between ionic current signal and polymer conformations, is thus essential for the successful identification of targets. Here, by analyzing ionic current traces of dsDNA translocation, we reveal that features up to now uniquely associated with knots are instead different structural motifs: plectonemes. By combining experiments and simulations, we demonstrate that such plectonemes form because of the solvent flow that induces rotation of the helical DNA fragment in the nanopore, causing torsion propagation outwards from the pore. Molecular dynamic simulations reveal that plectoneme nucleation is dominated by the applied torque, while the translocation time and size of the plectonemes depend on the coupling of torque and pulling force, a mechanism that might also be relevant for in vivo DNA organization. Experiments with nicked DNA constructs show that the number of plectonemes depends on the rotational constraints of the translocating molecules. Thus, our work introduces plectonemes as essential structural features that must be considered for accurate analysis of dsDNA polymers in the nanopore.http://doi.org/10.1103/spyg-kl86
spellingShingle Fei Zheng
Antonio Suma
Christopher Maffeo
Kaikai Chen
Mohammed Alawami
Jingjie Sha
Aleksei Aksimentiev
Cristian Micheletti
Ulrich F. Keyser
Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
Physical Review X
title Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
title_full Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
title_fullStr Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
title_full_unstemmed Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
title_short Torsion-Driven Plectoneme Formation During Nanopore Translocation of DNA Polymers
title_sort torsion driven plectoneme formation during nanopore translocation of dna polymers
url http://doi.org/10.1103/spyg-kl86
work_keys_str_mv AT feizheng torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT antoniosuma torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT christophermaffeo torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT kaikaichen torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT mohammedalawami torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT jingjiesha torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT alekseiaksimentiev torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT cristianmicheletti torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers
AT ulrichfkeyser torsiondrivenplectonemeformationduringnanoporetranslocationofdnapolymers