title: A hybrid computational model to explore the topological characteristics of epithelial tissues.
abstract: Epithelial tissues show a particular topology where cells resemble a polygon-like shape, but some biological processes can alter this tissue topology. During cell proliferation, mitotic cell dilation deforms the tissue and modifies the tissue topology. Additionally, cells are reorganized in the epithelial layer and these rearrangements also alter the polygon distribution. We present here a computer-based hybrid framework focused on the simulation of epithelial layer dynamics that combines discrete and continuum numerical models. In this framework, we consider topological and mechanical aspects of the epithelial tissue. Individual cells in the tissue are simulated by an off-lattice agent-based model, which keeps the information of each cell. In addition, we model the cell-cell interaction forces and the cell cycle. Otherwise, we simulate the passive mechanical behaviour of the cell monolayer using a material that approximates the mechanical properties of the cell. This continuum approach is solved by the finite element method, which uses a dynamic mesh generated by the triangulation of cell polygons. Forces generated by cell-cell interaction in the agent-based model are also applied on the finite element mesh. Cell movement in the agent-based model is driven by the displacements obtained from the deformed finite element mesh of the continuum mechanical approach. We successfully compare the results of our simulations with some experiments about the topology of proliferating epithelial tissues in Drosophila. Our framework is able to model the emergent behaviour of the cell monolayer that is due to local cell-cell interactions, which have a direct influence on the dynamics of the epithelial tissue.
authors.affiliation: Department of Mechanical Engineering, Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: González-Valverde
authors.affiliation: Department of Mechanical Engineering, Aragon Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain.
authors.forename: José Manuel
authors.identifier: 0000-0002-9864-7683
authors.initials: JM
authors.lastname: García-Aznar
mesh_terms: D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002450:Cell Communication; D002453:Cell Cycle; D049109:Cell Proliferation; D003198:Computer Simulation; D004848:Epithelium / Q000033:anatomy & histology*; D006801:Humans
keywords: agent-based model; cell cycle and cell proliferation; cell-cell interaction; emergent simulation of cell monolayers; finite element simulation; hybrid modelling