Physics in a nanopore microscope: Dynamics of polymers

Solid-state nanopores are ideally suited for the analysis of double-stranded nucleic acid structures. Here we design three-dimensional nucleic acid constructs that consist of DNA:DNA double strands [1] and RNA:DNA hybrids [2]. We ‘image’ the structured nucleic acids with our nanopore microscope with high-bandwidth ionic current detection.
We measured the translocation dynamics of RNA:DNA duplexes and B-form DNA:DNA molecules. Notably, RNA:DNA duplexes translocate through nanopores faster than DNA:DNA duplexes, despite containing the same number of base pairs while molecules with the same contour length have comparable velocity [3]. The measurements are used to disentangle the interactions of water, ions and molecules in the nanopore.
The ions and water flow in the nanopore should exert a torque on the double-helix during translocation. With the help of molecular dynamics and coarse-grained simulations in combination with extensive experimental data, we show that the torque induces super-coils and can be detected in nanopores [4]. This plectonemic supercoils can be mistaken for knots in the nanopore microscope. Finally, I will discuss implications for applications in rapid analysis of RNA and DNA.

References
[1] K. Chen et al., Nature Physics 17(9):1043-1049, 2021
[2] F. Bošković et al. Nature Chemistry 14:1258-1264, 2022
[3] F. Bošković et al., ACS nano 18(23):15013-15024, 2024.
[4] F. Zheng et al., Physical Review X, 15:031041,2025.