A quantitative high-resolution computational mechanics cell model for growing and regenerating tissues - Archive ouverte HAL Access content directly
Journal Articles Biomechanics and Modeling in Mechanobiology Year : 2019

A quantitative high-resolution computational mechanics cell model for growing and regenerating tissues

(1) , (2) , (2) , (3) , (4) , (2) , (3) , (3) , (5, 6)
1
2
3
4
5
6

Abstract

Mathematical models are increasingly designed to guide experiments in biology, biotechnology, as well as to assist in medical decision making. They are in particular important to understand emergent collective cell behavior. For this purpose, the models, despite still abstractions of reality, need to be quantitative in all aspects relevant for the question of interest. This paper considers as showcase example the regeneration of liver after drug-induced depletion of hepatocytes, in which the surviving and dividing hepatocytes must squeeze in between the blood vessels of a network to refill the emerged lesions. Here, the cells' response to mechanical stress might significantly impact the regeneration process. We present a 3D high-resolution cell-based model integrating information from measurements in order to obtain a refined and quantitative understanding of the impact of cell-biomechanical effects on the closure of drug-induced lesions in liver. Our model represents each cell individually and is constructed by a discrete, physically scalable network of viscoelastic elements, capable of mimicking realistic cell deformation and supplying information at subcellular scales. The cells have the capability to migrate, grow, and divide, and the nature and parameters of their mechanical elements can be inferred from comparisons with optical stretcher experiments. Due to triangulation of the cell surface, interactions of cells with arbitrarily shaped (triangulated) structures such as blood vessels can be captured naturally. Comparing our simulations with those of so-called center-based models, in which cells have a largely rigid shape and forces are exerted between cell centers, we find that the migration forces a cell needs to exert on its environment to close a tissue lesion, is much smaller than predicted by center-based models. To stress generality of the approach, the liver simulations were complemented by monolayer and multicellular spheroid growth simulations. In summary, our model can give quantitative insight in many tissue organization processes, permits hypothesis testing in silico, and guide experiments in situations in which cell mechanics is considered important.
Fichier principal
Vignette du fichier
Liedekerke2019_Article_AQuantitativeHigh-resolutionCo(1).pdf (11.51 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

hal-01956023 , version 1 (14-12-2018)
hal-01956023 , version 2 (06-02-2020)

Identifiers

Cite

Paul Van Liedekerke, Johannes Neitsch, Tim Johann, Enrico Warmt, Ismael Gonzàlez-Valverde, et al.. A quantitative high-resolution computational mechanics cell model for growing and regenerating tissues. Biomechanics and Modeling in Mechanobiology, 2019, ⟨10.1007/s10237-019-01204-7⟩. ⟨hal-01956023v2⟩
359 View
139 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More