MagPiezo: a Magnetogenetic Platform for Remote Activation of Endogenous Piezo1 Channels in Endothelial Cells
Susel Del Sol‐FernándeziD, Mariarosaria De SimoneiD, Yilian Fernández‐AfonsoiD, Daniel Garcia‐GonzaleziD, Pablo Martínez‐VicenteiD, Thomas S. van ZanteniD, Raluca M. FratilaiD, María MorosiD
Abstract
This work introduces MagPiezo, a novel magnetogenetic platform designed to enable remote and targeted manipulation of endogenous Piezo1 channels without genetic modification. MagPiezo integrates a custom-built magnetic applicator and 19 nm octahedral mixed ferrite nanoparticles (MFs) with enhanced magnetocrystalline anisotropy, engineered to selectively target Piezo1 channels. The application of a low intensity (< 40 mT), low frequency (1 Hz) magnetic field is sufficient to generate wireless torque forces in the piconewton range capable of gating Piezo1 channels in vitro. Remarkably, applying MagPiezo for short times (< 1 h) 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 both in vitro and in vivo.
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Claude Opus 5.5 · xhigh effort · 5 Nov 2026 · from the full text of version 1 (4 Jul 2025)
MagPiezo pairs 19 nm anti-Piezo1-conjugated ZnMnFe2O4 nanoparticles with a 1 Hz, <40 mT magnetic applicator to generate piconewton torque that gates endogenous Piezo1 channels in human endothelial cells.
Existing tools to activate mechanosensitive Piezo1 channels either lack molecular specificity and in vivo utility or require genetically engineered channels and 200-500 nm magnetic bead assemblies. Conjugating oriented anti-Piezo1 antibodies directly to 19 nm mixed-ferrite nanoparticles enables non-genetic, low-field magnetomechanical gating of native Piezo1.
Key results
ShownOctahedral Zn0.29Mn0.18Fe2.53O4 nanoparticles and a 4-axis 1 Hz magnetic applicator generated piconewton torque forces sufficient to gate Piezo1 at low magnetic fields.
The 19 ± 2 nm × 26 ± 3 nm nanoparticles had saturation magnetization of ~100 Am^2 kg^-1 and mass magnetic susceptibility of 3.8 × 10^-6 m^3 kg^-1; under a 1 Hz alternating field of 14-36 mT (77° rotation), single particles produced Fτ = 1.5 pN (τ1 = 2.0 × 10^-20 Nm) and 3 μm × 0.2 μm chains generated 9 - 40 pN (τassembly = 2.6 × 10^-16 Nm). · 2.1 Design and characterization of MagPiezo, a…
ShownMagPiezo stimulation selectively triggered sustained Ca2+ transients and cumulative Ca2+ influx in HUVECs via endogenous Piezo1 without inducing cytotoxicity or apoptosis.
Thirty-minute stimulation with MF@AbPIEZ (~2 oriented anti-Piezo1 antibodies per particle) increased Ca2+ events and cumulative flux versus field alone or isotype MF@AbIgG, was blocked by 5 μM GsMTx-4, and dropped by 54% in mean Ca2+ influx intensity and 51% in events per cell after Piezo1 siRNA knockdown (88% mRNA reduction at 72 h). · 2.2 Oriented conjugation of anti-Piezo1 Ab on MF…; 2.3 Real-time calcium dynamics after…
ShownMagnetomechanical Piezo1 activation remodeled the endothelial actin cytoskeleton and induced cell contraction within 20 minutes.
Twenty minutes of MagPiezo stimulation increased F-actin accumulation at cell edges and cell-cell contacts by nearly 40%, reduced HUVEC spread area from 920 ± 395 µm^2 to 549 ± 216 µm^2, and increased intense actin stress fibers in a GsMTx-4-sensitive manner. · 2.5.1 Magnetomechanical activation of Piezo1…
ShownMagPiezo stimulation drove nuclear translocation of c-Fos and upregulated endothelial mechanotransduction and angiogenesis transcripts.
Sixty minutes of MF@AbPIEZ + magnetic field exposure induced nuclear c-Fos accumulation in 61% of HUVECs (comparable to 66% in 20% FBS positive controls and blocked by GsMTx-4), and 20 minutes of stimulation significantly increased mRNA expression of VEGF-D, RHOA, PCNA, and NFkB (n = 4 biological replicates). · 2.5.2 c-Fos Activation as a readout of…; 2.5.3 Downstream effects of Piezo1 activation…; c-Fos immunofluorescence; RT-qPCR
Methods, data and reproducibility
Synthesized octahedral Zn0.29Mn0.18Fe2.53O4 nanoparticles by thermal decomposition, coated them with TAMRA-PMAO, and conjugated oriented polyclonal anti-Piezo1 cap-domain antibody (aa 2199-2426) and PEG (MF@AbPIEZ). Stimulated MF@AbPIEZ-treated HUVECs in a 4-set NdFeB servomotor applicator (14-36 mT, 1 Hz) and assayed Fluo-4 calcium imaging, siRNA knockdown, F-actin staining, c-Fos imaging, and RT-qPCR.
- In vitro HUVEC live-cell Fluo-4 calcium imaging, phalloidin F-actin remodeling, c-Fos nuclear translocation, and RT-qPCR assays · human · n = >50 cells/condition (Ca2+, n=4), 344-3072 cells (c-Fos, n=3), n=4 (RT-qPCR)
- Methods & tools
- MagPiezo, MagCalcium, COMSOL Multiphysics, Fiji, StackReg, Cell Profiler, Filament Sensor, CytExpert 2.4, Kaluza 2.1, GraphPad Prism 8
- Reagents & environment
- CytExpert 2.4, Kaluza 2.1, GraphPad Prism 8, Fiji with StackReg plugin, Cell Profiler, COMSOL Multiphysics (AC/DC Module), MagCalcium
- Reproducibility gaps
- Experimental imaging and RT-qPCR datasets are only available from the corresponding author upon reasonable request.
Limitations (3)
- All biological experiments were conducted in vitro in cultured HUVEC monolayers (passages 2 to 6); in vivo delivery, targeting specificity, and magnetomechanical activation were not tested. · stated by the authors
- Conjugating more than an average of two AbPIEZ antibody molecules per nanoparticle compromised the colloidal stability of the mixed ferrite dispersion. · stated by the authors
- Including more than six permanent magnets per actuator set in the custom magnetic applicator introduced mechanical vibrations into the cell culture. · stated by the authors
Who should read:Read this if you study mechanotransduction, Piezo1 ion channels, or magnetic nanoparticle actuators for remote non-genetic cell stimulation.
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