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

ABSTRACT: The dynamic mechanical response of tissues underlies their physiological function, yet direct, quantitative measurement of tissue stress in vivo has remained a major challenge. 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. Strikingly, abrupt stress increases, rather than cumulative or peak stress magnitude, determine EMT induction. Transcriptomic profiling reveals that gradual stress loading activates cytoprotective FOXO/AMPK pathways that reinforce epithelial stability, whereas acute stress surges overwhelm these defense mechanisms, predisposing cells to mesenchymal reprogramming. These findings establish the M3 sensor as a broadly applicable platform for linking tissue mechanics to cell-state transitions in development and disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE343051 | GEO | 2026/09/11

REPOSITORIES: GEO