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双纳米孔拔河中的DNA动力学

DNA Dynamics in Dual Nanopore Tug-of-War.

作者信息

Liu Zezhou, Dong Wangwei, St-Denis Thomas, Pessôa Matheus Azevedo Silva, Shiekh Sajad, Ravikumar Preethi, Reisner Walter

机构信息

Department of Physics, McGill University, Montréal, Québec.

出版信息

ArXiv. 2025 Aug 28:arXiv:2508.21144v1.

Abstract

Solid state nanopores have emerged as powerful tools for single-molecule sensing, yet the rapid uncontrolled translocation of the molecule through the pore remains a key limitation. We have previously demonstrated that an active dual-nanopore system, consisting of two closely spaced pores operated via feedback controlled biasing, shows promise in achieving controlled, slowed-down translocation. Translocation control is achieved via capturing the DNA in a special tug-of-war configuration, whereby opposing electrophoretic forces at each pore are applied to a DNA molecule co-captured at the two pores. Here, we systematically explore translocation physics during DNA tug-of-war focusing on genomically relevant longer dsDNA using a T-DNA model (166 kbp). We find that longer molecules can be trapped in tug-of-war states with an asymmetric partitioning of contour between the pores. Secondly, we explore the physics of DNA disengagement from a tug-of-war configuration, focusing on the dynamics of DNA free-end escape, in particular how the free-end velocity depends on pore voltage, DNA size and the presence of additional DNA strands between the pores (i.e. arising in the presence of folded translocation). These findings validate theoretical predictions derived from a first passage model and provide new insight into the physical mechanisms governing molecule disengagement in tug-of-war.

摘要

固态纳米孔已成为单分子传感的强大工具,但分子通过纳米孔的快速、不受控制的易位仍然是一个关键限制。我们之前已经证明,一种由两个紧密间隔的孔组成的有源双纳米孔系统,通过反馈控制偏置进行操作,在实现可控、减缓的易位方面显示出前景。易位控制是通过将DNA捕获在一种特殊的拔河配置中来实现的,即每个孔处相反的电泳力施加到共同捕获在两个孔处的DNA分子上。在这里,我们使用T-DNA模型(166 kbp)系统地探索DNA拔河过程中的易位物理,重点关注与基因组相关的更长的双链DNA。我们发现,更长的分子可以被困在拔河状态,孔之间的轮廓存在不对称分配。其次,我们探索DNA从拔河配置中脱离的物理过程,重点关注DNA自由端逃逸的动力学,特别是自由端速度如何取决于孔电压、DNA大小以及孔之间额外DNA链的存在(即在折叠易位存在时出现)。这些发现验证了从首次通过模型得出的理论预测,并为控制拔河中分子脱离的物理机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a355/12407631/f34e840d26a1/nihpp-2508.21144v1-f0001.jpg

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