Multicellular phase-field simulation on morphodynamics of growing cell assemblies

Sakurako Tanida^1,2, Kana Fuji¹, Tetsuya Hiraiwa^1,3*, Makiko Nonomura⁴, Masaki Sano^1,5

¹Universal Biology Institute, The University of Tokyo, Tokyo, Japan
²Department of Aeronautics and Astronautics, The University of Tokyo, Tokyo, Japan
³Institute of Physics, Academia Sinica, Taipei, Taiwan
⁴Department of Mathematical Information Engineering, Nihon University, Chiba, Japan
⁵Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai, China

* Presenter:Tetsuya Hiraiwa, email:thiraiwa@as.edu.tw

Growing cell assemblies cultured in vitro like organoids may serve as powerful systems for investigating the mechanisms that determine organ morphology. However, a comprehensive understanding of the general principles linking simple cellular behaviors to their overall morphology remains elusive. In this presentation, we will introduce our recent computational studies in which, based on a multicellular phase-field model, we simulate the morphology and morphodynamics of a cell assembly containing a fluid-filled cavity (lumen) grown from a few cells in vitro, like some organoids indeed, by focusing especially on lumen morphodynamics [1]. Our computational model accounts for multiple proliferating and growing cells, as well as lumens formed by these cells. It incorporates essential conditions such as timing and volume thresholds for cell division, rules for lumen nucleation, and luminal pressure. We will present the results demonstrating that simulations based on this model, starting from a few cells, autonomously generate a diverse range of morphological phenotypes depending on the luminal pressure and the minimum time required for the next cell division. We will compare a few simulation results with experimental observations of organoids and MDCK cysts [2]. References: [1] S. Tanida et al., "Predicting organoid morphology through a phase field model: insights into cell division and luminal pressure" PLOS Computational Biology 21, e1012090 (2025). [2] L. Lu et al. Nat. Commun. 16, 6307 (2025); B.-H. Lee et al. bioRxiv 10.1101/2024.05.29.596462

Keywords: Cell assembly, Organoid, Lumen, Multicellular phase-field model, Computer simulation