Susel Del Sol‐Fernández, Mariarosaria De Simone, Yilian Fernández‐Afonso, Daniel Garcia‐Gonzalez, Pablo Martínez‐Vicente, Thomas S. van Zanten, Raluca M. Fratila, María Moros
ABSTRACT This study introduces MagPiezo, a novel magnetogenetic platform designed to enable remote and targeted manipulation of endogenous Piezo1 channels without genetic modification in vitro. MagPiezo integrates a custom‐built magnetic applicator and 19 nm octahedral mixed ferrite nanoparticles (MF) with enhanced magnetocrystalline anisotropy, engineered to selectively target Piezo1 channels. The application of a low intensity (< 40 mT), low frequency (0.5 Hz) magnetic field is sufficient to generate wireless torque forces in the piconewton range capable of gating Piezo1 channels in vitro. Remarkably, MagPiezo induces robust responses in endothelial cells, including calcium influx, cytoskeletal reorganization and transcriptional activation. Unlike other magnetogenetic tools, MagPiezo avoids the need to assemble the magnetic nanoparticles (MNPs) into bigger beads to reach the opening threshold and does not need to genetically engineer Piezo1 channels. Moreover, it uses low magnetic field intensities and frequencies, enhancing its potential for in vivo translation. Therefore, MagPiezo is a powerful platform for manipulating Piezo1 channels and dissecting mechanotransduction events in vascular biology, paving the way for new strategies to modulate mechanoreceptors.