Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro

Significance Tumor growth intrinsically generates pressure onto the surrounding tissues, which conversely compress the tumor. These mechanical forces have been suggested to contribute to tumor growth regulation. We developed a microfluidic technique to produce 3D cell-based assays and to interrogate the interplay between tumor growth and mechanics in vitro. Multicellular spheroids are grown in permeable elastic capsules. Capsule deformation provides a direct measure of the exerted pressure. By simultaneously imaging the spheroid by confocal microscopy, we show that confinement induces a drastic cellular reorganization, including increased motility of peripheral cells. We propose that compressive stress has a beneficial impact on slowing down tumor evolution but may have a detrimental effect by triggering cell invasion and metastasis.