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Dynamics of driven polymer transport through a nanopore

Abstract

The transport of polymers across nanoscale pores underpins many biological processes, such as the ejection of bacteriophage DNA into a host cell and the transfer of genes between bacteria. The movement of polymers into and out of confinement is also the basis for a wide range of sensing technologies used for single-molecule detection and sequencing. Acquiring an accurate understanding of the translocation dynamics is an essential step in the quantitative analysis of polymer structure, including the localization of binding sites or sequences. Here we use synthetic nanopores and nanostructured DNA molecules to directly measure the velocity profile of driven polymer translocation through synthetic nanopores. Our results reveal a two-stage behaviour in which the translocation initially slows with time before accelerating close to the end of the process. We also find distinct local velocity correlations as the DNA polymer chain passes through the nanopore. Brownian dynamics simulations show that the two-stage behaviour is associated with tension propagation, with correlations arising from the random-walk conformation in which the DNA begins.

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Fig. 1: Translocation of dsDNA through synthetic nanopores is a non-equilibrium process.
Fig. 2: Schematic and examples of the measurement of DNA translocation velocity through synthetic nanopores.
Fig. 3: Intra-event motion correlation and cumulative spread in translocation time.
Fig. 4: Molecular origin of two stages of DNA velocity from simulations.
Fig. 5: Simulations show that correlated motion arises from initial distribution of DNA conformations.

Data availability

Source data are provided with this paper. Raw data of ionic current values for translocations together with a table summarizing all the nanopores used are available at https://doi.org/10.17863/CAM.69631.

Code availability

The code used for data collection and analysis and the code used for simulation analysis are available upon request from the corresponding author.

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Acknowledgements

This work was supported by an ERC consolidator grant (no. 647144) for N.A.W.B., K.C. and U.F.K. and a National Institute of Health grant (no. 5R01HG002776-15) for I.J. and M.M. N.E. acknowledges funding from the EPSRC; Cambridge Trust; and Trinity Hall, Cambridge.

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N.A.W.B., K.C. and U.F.K. designed the experiments. K.C., N.E. and N.A.W.B. performed the experiments. M.M. and I.J. performed the simulations. M.M., I.J. and N.A.W.B. analysed the simulation results. The paper was written through contributions of all the authors.

Corresponding author

Correspondence to Nicholas A. W. Bell.

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The authors declare no competing interests.

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Peer review information Nature Physics thanks Vincent Tabard-Cossa and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–34 and Tables 1–5.

Reporting Summary

Supplementary Video 1

Fifteen example simulations for translocations through a membrane geometry nanopore with the position of the tension front highlighted in green. The two frames show orthogonal viewpoints of the 3D simulation.

Source data

Source Data Fig. 1

Statistical source data.

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Fig. 5

Statistical source data.

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Chen, K., Jou, I., Ermann, N. et al. Dynamics of driven polymer transport through a nanopore. Nat. Phys. (2021). https://doi.org/10.1038/s41567-021-01268-2

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