Phenomenological modelling and simulation of cell clusters in 3D cultures.
Cell clustering and aggregation are fundamental processes in the development of several tissues and the progression of many diseases. The formation of these aggregates also has a direct impact on the oxygen concentration in their surroundings due to cellular respiration and poor oxygen diffusion through clusters. In this work, we propose a mathematical model that is capable of simulating cell cluster formation in 3D cultures through combining a particle-based and a finite element approach to recreate complex experimental conditions. Cells are modelled considering cell proliferation, cell death and cell-cell mechanical interactions. Additionally, the oxygen concentration profile is calculated through finite element analysis using a reaction-diffusion model that considers cell oxygen consumption and diffusion through the extracellular matrix and the cell clusters. In our model, the local oxygen concentration in the medium determines both cell proliferation and cell death. Numerical predictions are also compared with experimental data from the literature. The simulation results indicate that our model can predict cell clustering, cluster growth and oxygen distribution in 3D cultures. We conclude that the initial cell distribution, cell death and cell proliferation dynamics determine the size and density of clusters. Moreover, these phenomena are directly affected by the oxygen transport in the 3D culture.
Universidad de Zaragoza, Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, Campus Rio Ebro, 50018 Zaragoza, Spain; Instituto Químico Sarrià, Universidad Ramon Llul, Via Augusta, 390, 08017 Barcelona, Spain.
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González-Valverde
Instituto Químico Sarrià, Universidad Ramon Llul, Via Augusta, 390, 08017 Barcelona, Spain.
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Semino
Universidad de Zaragoza, Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, Campus Rio Ebro, 50018 Zaragoza, Spain. Electronic address: jmgaraz@unizar.es.
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García-Aznar
D001692:Biological Transport; D018929:Cell Culture Techniques; D016923:Cell Death; D049109:Cell Proliferation; D003198:Computer Simulation; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D018874:Spheroids, Cellular / Q000502:physiology*; D023822:Tissue Engineering
D010100:Oxygen
3D cell cluster; Hybrid model; Multi-physics model; Oxygen transport; Tissue engineering