Biological manipulation via physical stimuli such as light and magnetism has become a central goal in modern biotechnology. Among these modalities, magnetic fields offer unique advantages, including deep tissue penetration and untethered interventions in living systems. An ideal platform for such a magnetogenetic toolkit would be a genetically encodable protein with tunable magnetic features under physiological conditions. However, the development of such tools has been hindered by the lack of robust and stable protein scaffolds with strong intrinsic magnetic properties. Inspired by animal magnetoreception in nature, here, we rationally designed and systematically screened single-chain variants of the magnetoreceptor MagR. Through nine iterative rounds of design and experimental validation, we generated 25 constructs and ultimately identified a stable single-chain-dimer-based-tetramer, SDT-MagR, as the optimal magnetic molecular platform. This engineered protein exhibits exceptional structural stability and state-dependent magnetic behavior, showing ferrimagnetic-like characteristics in the solid state and paramagnetic behavior in solution. With enhanced magnetic susceptibility, purified SDT-MagR can be directly attracted by a magnet in vitro, establishing it as a promising new platform for future biomagnetic manipulation and magnetogenetics applications.
Zhang et al. (Fri,) studied this question.