Speaker
Description
Organoids are experimental model systems of organ development and function. They have recently gained considerable attention, as they provide insight into processes regulating development and regeneration in different tissues, and allow testing of treatment strategies for various pathogenic conditions. Pancreatic and liver-derived organoids in 3D culture display diverse dynamic behaviors. They grow into spherical epithelial monolayers, interact with the surrounding medium, secrete into an internal lumen, and can exhibit volume oscillations, fusion, drift, and rotational motion. To investigate which cell-level mechanisms, and their interactions, drive these behaviors, we analyzed 3D+t light sheet microscopy data. We employed organoid-level and nucleus segmentation, cell tracking, and 3D particle image velocimetry, to quantify size, morphology, volume oscillations, cell division dynamics, angular velocity, and drift. Using a mathematical approach, we derived a scaling law linking volume oscillations to cell division. We further developed an agent-based model incorporating mechanical cell-cell interactions, division, migration, mechanotransduction, polarity, and lumen pressure. The model reproduces the observed behaviors and enables systematic exploration of how complex organoid dynamics emerge from the interplay of fundamental cell-level mechanisms.
