Reconstructing the multicellular structure of a developing metazoan embryo with repulsion-attraction model and cell-cell connection atlas in vivo

Embryogenesis is a spatio-temporal multicellular evolutional process involved with intracellular biochemical activities and intercellular biophysical interactions. Reproducible and precise multicellular structures contribute to robustness of embryonic development by cell-cell communication, morphogenesis and other significant biological events. Using Caenorhabditis elegans as animal model, recently several researches established mechanical models to reconstruct the multicellular structures of this developmental system, in which cells interact via repulsive or attractive potentials inside an ellipsoidal eggshell. However, those models ignored some practical details and lack of test in depth. In this paper, we improved an in silico modeling framework based on previous models by revising formulae of interactive force and applying in vivo experimental information of eggshell shape, cell volume, cell position and cell-cell connection relationship. Cell pairs with and without empirically repeated connection were regarded to have different types of attractive force, which could help stabilize cells into their experimentally observed locations accompanied by correct neighbour relationships. Both previous models and our revised ones were tested, verified and compared to each other. Our modeling framework not only reproduces the multicellular structure patterns in an artificially compressed embryo with ∼50 cells, but also exhibits a potential to uncover active adjustments and controls on cell positioning.