TY - JOUR
T1 - Phenomenological modelling and simulation of cell clusters in 3D cultures
AU - González-Valverde, I.
AU - Semino, C.
AU - García-Aznar, J. M.
N1 - Funding Information:
This study is supported by the European Research Council (ERC) through project ( ERC-2012-StG 306571 ) and the Spanish Ministry of Economy and Competitiveness ( DPI2015-64221-C2-1-R ).
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - 3D cell cluster
KW - Hybrid model
KW - Multi-physics model
KW - Oxygen transport
KW - Tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=84986328585&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000384866000025&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.compbiomed.2016.08.019
DO - 10.1016/j.compbiomed.2016.08.019
M3 - Article
C2 - 27615191
AN - SCOPUS:84986328585
SN - 0010-4825
VL - 77
SP - 249
EP - 260
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
ER -