Compression-Induced Giant Vortex in a Human Breast Epithelial Spheroid

Coordinated vortex flows are a recurrent motif of living matter, appearing in systems from epithelial sheets to organoids and microbial colonies. Their ubiquity suggests a fundamental physical origin, yet how such flows emerge remains poorly understood. Prior studies have mainly examined cell-cell interactions within confined living matter, where viscoelasticity or plasticity of the surrounding medium modulates collective motion. Here, we report the emergence of a single giant vortex in non-tumorigenic breast epithelial spheroids under compression. Using a recently developed microfluidic rheometer (Suh et al., Lab Chip, 2025), spheroids were subjected to graded compressions (10–60%) for 48 hours. Digital image correlation revealed the emergence of coordinated vortical flow about the center of the spheroid, with the compression magnitude modulating the strength and coherence of these motions. Interestingly, this vortical flow was observed only in non-tumorigenic spheroids with strong E-cadherin-mediated adhesion and was absent in metastatic spheroids with weak cohesion. Using a 3D vertex model that couples cell polarity to neighbor alignment and includes cell-level stress, our simulations reproduce the emergence of vortex motion in a compressed spheroid. The modeling supports a stress-triggered mechanism whereby compression-induced stress promotes polarization alignment and rotation.  This work highlights how external mechanical stress regulates collective flow patterns in tumor spheroids, providing insight into tumor-ECM adaptation and the physical principles of cancer invasion.