Matrix Confinement Modulates 3D Spheroid Sorting and Burst-like Collective Migration

This study investigates how mechanical confinement within 3D matrices regulates cell sorting, jamming–unjamming transitions, and burst-like collective migration in heterogeneous tumor spheroids. By systematically tuning the stiffness of collagen–alginate hydrogels, the authors show that increased matrix confinement suppresses cell sorting and collective invasion, while softer matrices permit dynamic rearrangement and migratory bursts. These findings highlight the critical role of extracellular matrix mechanics in governing tumor organization and invasive behavior in 3D cancer models.