Abstract
Spheroids encapsulated within alginate capsules are emerging as suitable in vitro tools to investigate the impact of mechanical forces on tumor growth since the internal tumor pressure can be retrieved from the deformation of the capsule. Here we focus in particular on the Cellular Capsule Technology (CCT).
We show that a modeling approach accounting for the triphasic nature of the spheroid (it consists of extracellular matrix, tumor cells and interstitial fluid) offers a new perspective of analysis revealing that the pressure retrieved experimentally is representative of the average stress state in the multiphase continuum, so it cannot be interpreted as a direct picture of the pressure sustained by the tumor cells.
A multiphase reactive poro-mechanical model is cross-validated and proposed here as a suitable digital twin of the CCT experiment. Parameter sensitivity analyses on the digital twin allows us to show that the main parameters determining the encapsulated growth configuration are different from those which drive growth in free condition, confirming that radically different phenomena are at play. Multiphase reactive poro-mechanics emerges here as an exceptional theoretical framework to deeply understand CCT experiments, to confirm their hypotheses or further improve their design.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We introduced additional instructive explanations and better highlighted the core of this work. Sensitivity analysis has been done by the mean of first and second order Sobol indices.