What it is
Directly and quantitatively measuring the mechanical stress inside living tissue has remained a major challenge. The authors introduce the mechanoMR microparticle sensor: beads of alginate hydrogel (a water-rich gel) about 70 μm across, evenly embedded with zinc ferrite magnetic nanoparticles. When stress compresses a bead, its water content falls and protons diffuse less freely around the nanoparticles, which changes how quickly the magnetic resonance signal there decays (transverse relaxation), so that, once calibrated, the sensor measures local stress with single-particle resolution over a physiologically relevant range of 0 to 15 kPa. In tumour spheroids (small balls of tumour cells grown in the lab) and mouse xenografts (transplanted tumours growing in mice), it mapped tissue stress non-invasively, across space and over time, as the tumours progressed. The epithelial-mesenchymal transition (EMT, in which tightly joined epithelial cells take on a looser, migratory mesenchymal state) came with distinct patterns of stress remodelling in the living animals, and abrupt increases in stress, rather than cumulative or peak stress, determined whether EMT was induced.
Why it matters
In tumour models, abrupt rises in mechanical stress, not total or peak stress, determined whether cells underwent the epithelial-mesenchymal transition to a migratory state. Transcriptomic profiling (reading which genes are active) showed that gradual stress loading switches on cell-protecting FOXO and AMPK pathways that reinforce the epithelial state, whereas acute surges overwhelm these defences and predispose cells to mesenchymal reprogramming. Direct, quantitative measurement of stress inside living tissue had remained a major challenge, and the authors present the sensor as a broadly applicable platform for linking tissue mechanics to changes of cell state in development and disease.
Underlined numbers link to their source. Every metric and quoted figure is listed under Sources and data below.
Filed underCellular Mechanics and Interactions, Hydrogels: synthesis, properties, applications, Cancer Cells and Metastasis