Active rheology shapes collective flows in uniaxially compressed 3D spheroids

Abstract

How compression changes both the magnitude and organization of cell motion remains unclear. Using a three-dimensional active vertex model, we examine how tissue state and active dynamics shape the response of confined spheroids to uniaxial compression. With polarity alignment switched off, compression enhances transverse motion in solid-like spheroids throughout the tested activity range, whereas the fluid-like response reverses from acceleration at low activity to slowing at high activity. Changes in contact persistence organize these responses along a common empirical trend. Passive five-cell calculations reveal how compression reshapes local rearrangement barriers: the response depends on geometry and loading direction, and a high-strain increase in the fluid-like mean coexists with many low-barrier paths. In a separate high-alignment regime, strong compression induces coherent rotation in solid-like spheroids, while fluid-like spheroids show no comparable collective rotation. The rotating solids have a higher contact-persistence index than the fluids and exhibit tangential peripheral cell organization. Controlled perturbations reveal compression-induced softening of a differential-twist mode and slower relaxation with activity. Together, these results identify an activity-dependent reversal of the motility response and compression-induced coherent rotation as two distinct outcomes of loading, linking them to contact persistence, local rearrangement costs, and active coordination.