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

TLDR

Tumor growth generates pressure on surrounding tissues, compressing the tumor, and these mechanical forces are thought to influence tumor growth regulation. The study develops a microfluidic technique to produce 3D cell‑based assays for probing the interaction between tumor growth and mechanical forces in vitro. Multicellular spheroids are grown in permeable elastic capsules, whose deformation directly measures the exerted pressure. Confocal imaging revealed that confinement induces extensive cellular reorganization and increased peripheral cell motility, indicating that compressive stress can slow tumor evolution while also promoting invasion and metastasis.

Abstract

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.