Tumour growth: Bayesian parameter calibration of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment

Author:

Hervas-Raluy SilviaORCID,Wirthl BarbaraORCID,Guerrero Pedro E.,Rei Gil Robalo,Nitzler Jonas,Coronado Esther,De Mora Sainz Jaime Font,Schrefler Bernhard A.,Gomez-Benito Maria JoseORCID,García-Aznar Jose Manuel,Wall Wolfgang A.

Abstract

AbstractTo unravel processes that lead to the growth of solid tumours, it is necessary to link knowledge of cancer biology with the physical properties of the tumour and its interaction with the surrounding microenvironment. Our understanding of the underlying mechanisms is however still imprecise. We therefore developed computational physics-based models, which incorporate the interaction of the tumour with its surroundings based on the theory of porous media. However, the experimental validation of such models represents a challenge to its clinical use as a prognostic tool. This study combines a physics-based model with in vitro experiments based on microfluidic devices used to mimic a 3D tumour microenvironment. By conducting a global sensitivity analysis, we identify the most influential input parameters and infer their posterior distribution based on Bayesian calibration. The resulting probability density is in agreement with the scattering of the experimental data and thus validates the modelling approach. Using the proposed workflow, we demonstrate that we can indirectly characterise the mechanical properties of neuroblastoma spheroids that cannot feasibly be measured experimentally.

Publisher

Cold Spring Harbor Laboratory

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