Cell spheroid viscoelasticity is deformation-dependent

Abstract Tissue surface tension influences cell sorting and tissue fusion. Earlier mechanical studies suggest that multicellular spheroids actively reinforce their surface tension with applied force. Here we study this open question through high-throughput microfluidic micropipette aspiration measurements on cell spheroids to identify the role of force duration and cell contractility. We find that larger spheroid deformations lead to faster cellular retraction once the pressure is released, regardless of the applied force and cellular contractility. These new insights demonstrate that spheroid viscoelasticity is deformation-dependent and challenge whether surface tension truly reinforces.