Biofunctional coating of synthetic magnetic nanoparticles enables magnetogenetic control of protein functions inside cells

Remote control of cellular functions via magnetic forces offers unique opportunities in fundamental research and biomedical application. Intracellular delivery of functionalized magnetic nanoparticles (MNP) provides versatile opportunities to assemble signalling platforms for spatiotemporal control by magnetic forces. Such magnetogenetic application, however, has remained highly challenging due to a lack of MNP providing suitable biological, physicochemical and magnetic properties. Here, we achieved single-step surface coating of synthetic maghemite core nanoparticles with green fluo-rescent protein fused to the iron binding site of Mms6 from magnetotactic bacteria. We yielded MNP with intracellular stealth properties (syMagIcS), which could be readily biofunctionalized in situ and translocated within cells via magnetic field gradients. We successfully exploited syMagIcS for spati-otemporal control of Rac1 signalling at the plasma membrane via its guanine nucleotide exchange factor protein TIAM1 and for spatial control of liquid-liquid phase separation using the intrinsically disordered domain of the protein DDX4.