Submolecular modulation of PIEZO1 mechanotransduction with wireless tailor-made nanoswitches
Year: 2026
Type: article
Abstract: PIEZO mechanoreceptors play critical roles in fundamental physiological processes such as proprioception or musculoskeletal biomechanics. However, their complex gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective probing tools. Here, we combine molecular imprinting and magnetic concepts to develop tailor-made nanoswitches enabling wireless targeted actuation of PIEZO1. Two epitopes selected in silico from distinct domains of PIEZO1 were used as templates for synthesizing magnetically responsive molecularly imprinted nanoparticles. These nanoswitches showed sub-nanomolar affinity for their respective epitope and recognized PIEZO1 in endothelial cells, similarly to antibodies. Applying magnetic fields to actuate PIEZO1 through nanoswitches led to increased calcium signaling, Yes-associated protein (YAP) nuclear translocation, and significant changes in the expression of genes related to PIEZO1 activity, implying that they can transduce the stimulus into intracellular signaling effects. Finally, this wireless actuation system proved to be effective in differentially modulating the behavior of mesenchymal stem cells. Remarkably, the selective targeting of each epitope led to contrasting downstream signaling cascades, implying distinct roles for each superstructure domain in the sophisticated function of these channels. Overall, this technology constitutes a promising tool for studying PIEZO-mediated mechanobiology, opening perspectives for harnessing its potential toward therapeutic approaches. • Magnetic nanoswitches were molecularly imprinted to target and wirelessly actuate PIEZO1 with sub-nanomolar affinity. • Specific actuation of PIEZO1 via nanoswitches triggers cell mechanotransduction and alters downstream gene expression. • Targeting different PIEZO1 domains induces distinct cellular responses, highlighting domain-specific roles. • Tailor-made nanoswitches offer a novel, efficient approach for dissecting PIEZO1’s complex mechanobiology.
Source: Bioactive Materials
Institutions: International Iberian Nanotechnology Laboratory, 3B's Research Group, University of Minho, Universidade de Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago, University of Zurich, ETH Zurich, Universitätsklinik Balgrist, Institute for Biomechanics, Universidade do Porto, Instituto de Ciências Biomédicas Albel Salazar
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,200
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Xunta de Galicia, Horizon 2020 Framework Programme, HORIZON EUROPE Framework Programme, European Research Council, Fundação para a Ciência e a Tecnologia, Agencia Estatal de Investigación, European Social Fund
Awards: G1254518699, G1521263816, G1686559485, Novo: Molecular imprinting technologies for growth factor sequestration and control of stem cell fate in tendon regeneration Antigo: Magnetic-based tissue engeneering approaches for tendon regeneration, G2779382418, G3661974067, G4096995376, G493133315, G5156987912, G5587996612, TendO2n: targeting hypoxia signaling to combat human tendon disease, G737327039
OpenAlex ID: W7156164668