Mechanical stress remodeling drives epithelial-mesenchymal transition in the tumor microenvironment

Here, we introduce the mechanoMR microparticle (M³) sensor, a platform that transduces local tissue mechanical stress into quantitative magnetic resonance (MR) readouts with single-particle resolution. The sensor comprises alginate hydrogel microparticles (~70 μm) homogeneously embedded with Zn₀.₄Fe₂.₆O₄ 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 quantitative measurement of local tissue stress over a physiologically relevant range of 0-15 kPa. We demonstrate the platform in tumor spheroids and mouse xenografts, enabling non-invasive, spatiotemporal mapping of tissue stress during tumor progression. Using this approach, we show that epithelial-mesenchymal transition (EMT) is accompanied by distinct stress-remodeling patterns in vivo.