Finite element simulations drive the design of in vitro models of down-scaled crosstalk in oxygen metabolism

Introduction Engineering biological communities enables the investigation of behavioural patterns driven by inter- individual crosstalk across scales. Nevertheless, biomedicine could take advantage of this modelling framework to buffer phenotypic readouts from potential coexistence-related biases. Methods To explore this concept, here we used finite element models to probe oxygen consumption in multi-spheroid systems and understand whether they can constitute reliable models of coexistence in vitro (or in vitro ecosystems), by quantifying how individual metabolism is influenced by the number, size and spatial distribution of cell constructs as determinants of supplied oxygen levels. Then, we adapted one of the simulated configurations experimentally to provide a first proof of prediction consistency resorting to a rigorous method for metabolic characterization in vitro that we previously established. Results Computational and experimental outcomes display similar trends. Albeit a systematic validation of numerical predictions is still to be performed, such results coherently indicate a modulation of oxygen consumption driven by the local availability. Discussion These models may set the foundations to better understand cell-cell or organoid-organoid crosstalk and how it affects in vitro assays typically evaluated in coexisting cellular samples – such as pre-clinical testing for drug development – as well as be even extended to ecological sciences to assess the impact of resource sharing in the presence of heterogeneities and environmental disturbances.