Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

Abstract Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed...

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Autores principales:	Yoshifumi Asakura, Yohei Kondo, Kazuhiro Aoki, Honda Naoki
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1f36c1201644cd48beb2191533f33ab
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spelling	oai:doaj.org-article:a1f36c1201644cd48beb2191533f33ab2021-12-02T10:54:15ZHierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue10.1038/s41598-021-83396-62045-2322https://doaj.org/article/a1f36c1201644cd48beb2191533f33ab2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83396-6https://doaj.org/toc/2045-2322Abstract Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.Yoshifumi AsakuraYohei KondoKazuhiro AokiHonda NaokiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshifumi Asakura Yohei Kondo Kazuhiro Aoki Honda Naoki Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
description	Abstract Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.
format	article
author	Yoshifumi Asakura Yohei Kondo Kazuhiro Aoki Honda Naoki
author_facet	Yoshifumi Asakura Yohei Kondo Kazuhiro Aoki Honda Naoki
author_sort	Yoshifumi Asakura
title	Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
title_short	Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
title_full	Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
title_fullStr	Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
title_full_unstemmed	Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
title_sort	hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a1f36c1201644cd48beb2191533f33ab
work_keys_str_mv	AT yoshifumiasakura hierarchicalmodelingofmechanochemicaldynamicsofepithelialsheetsacrosscellsandtissue AT yoheikondo hierarchicalmodelingofmechanochemicaldynamicsofepithelialsheetsacrosscellsandtissue AT kazuhiroaoki hierarchicalmodelingofmechanochemicaldynamicsofepithelialsheetsacrosscellsandtissue AT hondanaoki hierarchicalmodelingofmechanochemicaldynamicsofepithelialsheetsacrosscellsandtissue
_version_	1718396486319865856

Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

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