The outcome...

the mechanical stress induced by an expanding multicellula

Measuring the Mechanical Stress Induced by an Expanding

Rapid volumetric growth and extensive invasion into brain parenchyma are hallmarks of malignant neuroepithelial tumors in vivo. Little is known, however, about the mechanical impact of the growing brain tumor on its microenvironment. To better understand the environmental mechanical response, we used multi-particle tracking and microrheological methods to probe the environment of a dynamically expanding, multicellular brain tumor spheroid that grew for six days in a three-dimensional Matrigel-based in vitro assay containing 1.0 m latex beads. These beads act as reference markers for the gel, allowing us to image the spatial displacement of the tumor environment using high-resolution timelapse video-microscopy. The results show that the volumetrically expanding tumor spheroid pushes the gel outward and that this tumor-generated pressure propagates to a distance greater than the initial radius of the tumor spheroid. Intriguingly, beads near the tips of invasive cells are displaced inward, towards the advancing invasive cells. Furthermore, this localized cell traction correlates with a marked increase in total invasion area over the observation period. This case study presents evidence that an expanding microscopic tumor system exerts both significant mechanical pressure and significant traction on its microenvironment