Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction.

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.

Density-Polarity Coupling in Confined Active Polar Films: Asters, Spirals, and Biphasic Orientational Phases.

Topological defects in active polar fluids can organize spontaneous flows and influence macroscopic density patterns. Both of them play an important role during animal development. Yet the influence of density on active flows is poorly understood. Motivated by experiments on cell monolayers confined to disks, we study the coupling between density and polar order for a compressible active polar fluid in the presence of a +1 topological defect. As in the experiments, we find a density-controlled spiral-to-aster transition. In addition, biphasic orientational phases emerge as a generic outcome of such coupling. Our results highlight the importance of density gradients as a potential mechanism for controlling flow and orientational patterns in biological systems.