Cell Centred Finite Element Model for Intestinal Organoids Shape Analysis: From tissue architecture to mechanics

Abstract

Organoids, established from stem cells owing to their self-renewal and differentiation capacities, are self-organised three-dimensional tissue culture recapitulating the original cell populations and their associated functions, as well as tissue architecture. The intestinal organoids established from adult stem cells isolated from the intestinal crypts, recreate 3D epithelial mini-intestines. They represent an excellent tool to study intestinal stem cell capacities and their ability to reconstitute a fully polarised and functional epithelium. These 3D cultures recapitulate in vitro the tissue characteristics, including architecture, either in physiological or disease conditions whether they are established from healthy or pathological tissue samples respectively. In this regard, their use for potential treatments screening carries the hopes for a future personalized medicine for which image-analysis such as HCS are increasingly being developed. Numerous numerical models have been developed to study the effects of organoid development on their shape. Most of them remain mainly restricted in their physical description due to the complex inter-relationship between cell physics, phenotypes and behaviors, exploding the number of variables in modeling formulation. Finite Element Method (FEM) is a numerical analysis method employed in mechanics to model deformation and evaluate residual stress of complex structures making it difficult to obtain analytical solutions. Considering epithelial architecture as a homogeneous material where each cell is an elemental equivalent part of the problem, FEM allows a direct link between tissue architecture deformations and local mechanical constraints. Here we formalise a new organoid cell centred FEM with a physical description borrowed from the engineering world. This model can allow a better understanding of the individual contribution of physical/mechanical properties of individual cells on general tissue architecture. Author SummaryStem cell research has experienced a breakthrough with the development of powerful tools, namely, organoids. The possibility to recreate in vitro from adult stem cells a fully functional adult tissue with its actual 3D architecture made accessible poorly defined steps in tissue morphogenesis or pathophysiology. If recent efforts have focused on studies of tissue specific organoids functions, modelling a generic bio-mechanic model of organoid remains necessary to decipher the mechanical biodiversity of organoid structures.