Mechanical stress remodelling drives epithelial-mesenchymal transition in the tumour microenvironment

The dynamic mechanical response of tissues underlies their physiological function; yet a direct, quantitative measurement of tissue stress in vivo has remained a major challenge. Here we introduce the mechanoMR microparticle sensor, a platform that transduces local tissue mechanical stress into quantitative magnetic resonance read-outs with single-particle resolution. The sensor comprises alginate hydrogel microparticles (~70 μm) homogeneously embedded with Zn_0.4Fe_2.6O₄ magnetic nanoparticles, where stress-induced hydrogel compression reduces local water content and restricts proton diffusion surrounding the magnetic nanoparticles, thereby modulating magnetic-nanoparticle-mediated transverse relaxation (R₂). Calibration of the stress-R₂ relationship enables a quantitative measurement of local tissue stress over a physiologically relevant range of 0-15 kPa. We demonstrate the platform in tumour spheroids and mouse xenografts, enabling the non-invasive, spatiotemporal mapping of tissue stress during tumour progression. Using this approach, we show that epithelial-mesenchymal transition is accompanied by distinct stress remodelling patterns in vivo. Strikingly, abrupt stress increases, rather than cumulative or peak stress magnitude, determine epithelial-mesenchymal transition induction. Transcriptomic profiling reveals that gradual stress loading activates cytoprotective FOXO/AMPK pathways that reinforce epithelial stability, whereas acute stress surges overwhelm these defence mechanisms, predisposing cells to mesenchymal reprogramming. These findings establish the mechanoMR microparticle sensor as a broadly applicable platform for linking tissue mechanics to cell-state transitions in development and disease.