Mathematical formulation and parametric analysis of in vitro cell models in microfuidic devices: application to diferent stages of glioblastoma evolution

Abstract

In silico models and computer simulation are invaluable tools to better understand complex biological processes such as cancer evolution. However, the complexity of the biological environment, with many cell mechanisms in response to changing physical and chemical external stimuli, makes the associated mathematical models highly non-linear and multiparametric. One of the main problems of these models is the determination of the parameters’ values, which are usually ftted for specifc conditions, making the conclusions drawn difcult to generalise. We analyse here an important biological problem: the evolution of hypoxia-driven migratory structures in Glioblastoma Multiforme (GBM), the most aggressive and lethal primary brain tumour. We establish a mathematical model considering the interaction of the tumour cells with oxygen concentration in what is called the go or grow paradigm. We reproduce in this work three diferent experiments, showing the main GBM structures (pseudopalisade and necrotic core formation), only changing the initial and boundary conditions. We prove that it is possible to obtain versatile mathematical tools which, together with a sound parametric analysis, allow to explain complex biological phenomena. We show the utility of this hybrid “biomimetic in vitro-in silico” platform to help to elucidate the mechanisms involved in cancer processes, to better understand the role of the diferent phenomena, to test new scientifc hypotheses and to design new data-driven experiments.