Speaker
Description
The reciprocal interactions between ionising radiation (IR) and glucose metabolism in mammalian cells have gained interest over these last decades. While reactive oxygen species (ROS) and HIF-1α emerge as key mediators in these interactions, the influence of ROS on HIF-1α following irradiation is still being debated. Different types of intermediate entities between ROS and HIF-1α have been proposed, each with different modes of action. In this study we propose to identify potential intermediates through their mode of action for several cell types studied in the literature. This is realized by reproducing the measured dynamics of key metabolic proteins following IR, specifically the LDH protein involved in glycolysis or ATP dynamics experimentally measured in cell cultures. These findings are then transposed in a tissue scale model – the spheroid – that allows to address the metabolic interactions between cells. To that end, a hybrid multiscale model based on the PhysiCell framework has been developed. It integrates individual cell metabolic states – previously defined - and incorporate cell-cell interactions in relation to the evolving environmental conditions for the spheroid exposed to IR. In light of the identified ROS-HIF relationships, our model aims to gain insight into the metabolic dynamics within an irradiated spheroid - dynamics which could be observed in future experiments.
