Abstract
There is considerable interest in the ability to modulate biological processes with magnetic fields. Here we demonstrate a strategy for selecting aptamers that exhibit enhanced binding to paramagnetic metal ions under a strong magnetic field. Using a high-magnetic-field (HM)-SELEX method targeting Co2+, we identified two classes of aptamers with magnetically-modulated binding behavior. One displayed a gradual 2–3-fold increase in affinity as magnetic field strength increased, while the other went from minimal target binding at ambient field strength to an affinity of ~200 μM at ≥ 6 T. Molecular simulations revealed that the magnetic field induces a global conformational rearrangement by enhancing aptamer-metal electrostatic interactions, optimizing the coordination geometry of the nucleotides. Chemical footprinting and mutational analysis confirmed the role of certain conformational changes in magnetically-induced ion binding. These results suggest opportunities to generate aptamer switches that can be used to manipulate biorecognition processes via an externally applied magnetic field in diverse applications.
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Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. The high-throughput sequencing data generated in this study have been deposited in the NCBI Gene Expression Omnibus database under accession code PRJNA1395820. The source data generated in this study are provided in the Source Data file. Source data are provided with this paper.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (U23A20265, 32072306 to L.Z.), and the Anhui Provincial Natural Science Foundation (2408085MC072 to L.W.). We thank the staff members of the SM1 superconducting magnet (https://cstr.cn/31125.02.SHMFF.SM1.MG) at the Steady High Magnetic Field Facility, CAS (https://cstr.cn/31125.02.SHMFF), for providing technical support and assistance. The analysis work of this article was partially carried out at the Instrumental Analysis Center, Hefei University of Technology.
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Conceptualization: L.W., H.T.S., and L.Z. Methodology: S.G., L.W., Y.M., H.T.S., and L.Z. Investigation and Validation: S.G. and L.Y. Visualization: S.G. Data Curation: S.G. and L.Y. Formal analysis: S.G. and L.W. Resources: L.W., Y.M., and L.Z. Writing—Original Draft: S.G. and L.W. Writing—review & Editing: S.G., L.W., M.E., H.T.S,. and L.Z. Supervision, Project administration: L.W., H.T.S., and L.Z. Funding acquisition: L.W. and L.Z. All authors have read and agreed to the submitted version of the manuscript.
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S. G., L. W., and L. Z. are inventors on a patent granted to Hefei University of Technology related to the screening of magnetic-sensitive aptamers for Co2+ (application number 202510331988.8). The remaining authors declare no competing interests.
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Gao, S., Wang, L., Yao, L. et al. Aptamers with magnetically tunable affinity for divalent cobalt ions. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70871-9
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DOI: https://doi.org/10.1038/s41467-026-70871-9
