Aptamers with magnetically tunable affinity for divalent cobalt ions

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.