[C02] Developmental Biology

[C02-02] Emergence of diverse morphologies of multicellular systems based on inferred cell-cell interaction forces

*Koyama Hiroshi^1,2, Toshihiko Fujimori^1,2 (1. Div. Embryology, National Institute for Basic Biology (Japan), 2. SOKENDAI (Graduate Univ. Advanced Studies) (Japan))

Keywords:

image-based force inference,particle model,early embryogenesis,cell-cell interaction

During the development of multicellular systems, mechanical features of cells are fundamental parameters for morphogenesis. To quantitatively assess the mechanical forces driving morphogenesis, we developed an image-based method for statistically inferring mechanical forces of cells (Koyama et al. 2023). In this method, a cell is approximated as a point particle, and this model is fitted to nuclear tracking data obtained from live microscopic imaging. This approach enables us to quantify attractive and repulsive forces of cell–cell interactions. First, by applying this method to synthetic data generated by the vertex model, we found that cell-cell adhesive forces contribute to attractive, whereas cell-cell junction tensions lead to repulsion in epithelial cell sheets (Koyama et al. 2025). An abrupt change in the profiles of the attractive/repulsive forces was detected during solid-liquid transition of tissues. Additionally, these effective forces were modulated by external structures such as the extracellular matrix and liquid cavities. By applying our method to early embryogenesis in mice and C. elegans, we successfully obtained 4D (xyzt)-force maps, revealing differences in attractive and repulsive force properties across cell types and developmental stages. To evaluate the functional significance of these changes, we performed simulations that successfully recapitulated key morphological features observed in mouse and C. elegans embryos. Further theoretical analyses identified mechanical features which critically contribute to morphological varieties (Koyama et al. 2024). These results indicate that the mechanical properties based on the attractive/repulsive forces govern diverse morphologies during early embryogenesis. Our precise quantification of the cell-cell interaction forces highlights their critical roles in the emergent properties of cells for morphogenesis.