@article {Asakura859348, author = {Yoshifumi Asakura and Yohei Kondo and Kazuhiro Aoki and Honda Naoki}, title = {Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue}, elocation-id = {859348}, year = {2019}, doi = {10.1101/859348}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Chemical and mechanical properties on a tissue regulate cellular migration. The orchestrated collective cell migration is a fundamental process in embryonic development and tissue homeostasis. Intra-cellular chemical signal network has been revealed by molecular biological researches, but there remains a fundamental question how the cell population level phenomenon is emerged across the hierarchy from the single-cell level process. However, there is a huge gap in our understanding between the microscopic single-cell behavior and macroscopic multicellular dynamics. To fill the hierarchical gap, we have focused on a wound healing experimental system in which ERK propagating wave from the wound edge mediates collective cell migration in the opposite direction. To reveal the mechanisms in which cellular dynamics causes tissue dynamics, here we proposed a hierarchical framework utilizing continuum dynamics formulation. Our continuum model recapitulated the cell migration observed in experiments to an opposite direction of ERK waves, and we confirmed a consistency with our previous single-cellular dynamics model. Here, our new model showed the mechanisms by which the collective tissue behavior emerges at the cell population level. Therefore, this approach allows us to seamlessly connect the hierarchical causality from single-cell level to tissue level.}, URL = {https://www.biorxiv.org/content/early/2019/11/29/859348}, eprint = {https://www.biorxiv.org/content/early/2019/11/29/859348.full.pdf}, journal = {bioRxiv} }