Predicting organoid morphology through a phase field model: Insights into cell division and lumenal pressure

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sakurako Tanida - , The University of Tokyo (Author)
  • Kana Fuji - , The University of Tokyo (Author)
  • Linjie Lu - , University of Strasbourg (Author)
  • Tristan Guyomar - , University of Strasbourg (Author)
  • Byung Ho Lee - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Alf Honigmann - , Clusters of Excellence PoL: Physics of Life, Chair of Biophysics, Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Anne Grapin-Botton - , Max Planck Institute of Molecular Cell Biology and Genetics, Clusters of Excellence PoL: Physics of Life (Author)
  • Daniel Riveline - , University of Strasbourg (Author)
  • Tetsuya Hiraiwa - , The University of Tokyo, National University of Singapore, Academia Sinica - Institute of Physics (Author)
  • Makiko Nonomura - , Nihon University (Author)
  • Masaki Sano - , The University of Tokyo, Shanghai Jiao Tong University (Author)

Abstract

Organoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.

Details

Original languageEnglish
Article numbere1012090
JournalPLOS computational biology
Volume21
Issue number8
Publication statusPublished - Aug 2025
Peer-reviewedYes

External IDs

ORCID /0000-0003-0475-3790/work/190571450