Compaction dynamics during progenitor cell self-assembly reveal granular mechanics

We study the self-assembly dynamics of human progenitor cells in agarose micro-wells that are used for production of chondrogenic organoids. Using image analysis on time-lapse microscopy, we estimate the aggregate area in function of time for a large number of aggregates. In control conditions, the aggregate radius follows an exponential relaxation that is consistent with the dewetting dynamics of a liquid film. Introducing Y-27632 Rho kinase inhibitor, the compatibility with the liquid model is lost, and slowed down relaxation dynamics are observed. We demonstrate that these aggregates behave as granular piles undergoing compaction, with a density relaxation that follows a stretched exponential. Using simulations with an individual cell-based model, we construct a phase diagram of cell aggregates that suggests that the aggregate in presence of Rho kinase inhibitor approaches the glass transition.