We are glad to share a new research, published in Advanced Functional Materials! 🚀
How can we remotely trigger cell signaling and accelerate cell proliferation without using drugs? In our study, “Remote activation of Wnt signaling and cell proliferation by E-cadherin magnetomechanical stimulation”, we introduce a novel magnetogenetic strategy to remotely tune the Wnt/ β-catenin pathway using magnetic nanoparticles and low-intensity magnetic fields.
💡 The challenge: The Wnt/ β-catenin pathway is a crucial master regulator of cell proliferation and tissue repair. However, conventional chemical approaches lack spatiotemporal control and often trigger off-target effects.
🧲 Our solution
We functionalized magnetic nanoparticles (MNPs) with the full extracellular domain of E-cadherin to selectively bind cellular E-cadherin molecules on epithelial cells. Exposing the labeled cells to a weak, dynamic magnetic field (~33 mT) generates localized forces directly on E-cadherin! This gentle mechanical force induces β-catenin release from the membrane complex, activating Wnt target genes, translating into enhanced cell proliferation and significantly accelerated epithelial gap closure without adverse cytotoxic effects.
🌟 Why it matters: Unlike previous designs, this platform provides a purely mechanical and targeted input, offering a non-invasive and highly adaptable strategy for probing mechanobiology and guiding targeted regenerative therapies.
Congratulations to all the team, but especially to Christian Castro Hinojosa, how has worked really hard to publish this work, a major milestone of our ERC Starting Grant project SIROCCO!
Remote activation of Wnt signaling and cell proliferation by e-cadherin magnetomechanical stimulation
DOI: 10.1002/adfm.78964D
Advanced Functional Materials, 2026; 0:e78964; 15th Oct. 2026
Christian Castro-Hinojosa, Pablo Martínez-Vicente, Lucía G. Recaredo, Susel Del Sol-Fernández, Pilar Gomollón-Zueco, Yilian Fernández-Afonso, Raluca M. Fratila, María Moros
Abstract:
The ability to remotely and precisely manipulate intracellular signaling pathways is crucial for fundamental research and therapeutics. The Wnt/β-catenin cascade regulates cell proliferation, differentiation, and tissue regeneration, but current pharmacological activation methods lack spatiotemporal control and induce off-target effects. Here, we introduce a pioneering magnetogenetic toolkit to modulate the Wnt/β-catenin pathway through magnetomechanical stimulation of E-cadherin, a key cell adhesion molecule intimately linked to β-catenin dynamics. Magnetic nanoparticles functionalized with the extracellular domain of E-cadherin (MNPs@E/EC15) selectively bind cellular E-cadherins. Applying a low-intensity, low-gradient magnetic field via a custom stimulator generates localized mechanical forces that trigger E-cadherin mechanotransduction. This stimulation induces β-catenin membrane release, nuclear translocation, and Wnt target gene activation, confirmed by transcriptomic profiling and a luciferase reporter assay. These molecular changes translate into enhanced cell proliferation and accelerated gap closure. This work establishes an innovative, non-invasive tool for probing E-cadherin mechanobiology and remotely modulating Wnt/β-catenin signaling. Unlike other mechanotransduction tools, this approach enables simultaneous, high-spatiotemporal modulation of multiple cells using low-intensity magnetic fields adaptable for in vivo designs. Our findings open promising avenues for studying mechanotransduction and developing targeted regenerative therapies based on mechanical stimulation.
