A mathematical model for selective differentiation of neural progenitor cells on micropatterned polymer substrates

The biological hypothesis that the astrocyte-secreted cytokine, interleukin-6 (IL6), stimulates differentiation of adult rat hippocampal progenitor cells (AHPCs) is considered from a mathematical perspective. The proposed mathematical model includes two different mechanisms for stimulation and is based on mass–action kinetics. Both biological mechanisms involve sequential binding, with one pathway solely utilizing surface receptors while the other pathway also involves soluble receptors. Choosing biologically-reasonable values for parameters, simulations of the mathematical model show good agreement with experimental results. A global sensitivity analysis is also conducted to determine both the most influential and non-influential parameters on cellular differentiation, providing additional insights into the biological mechanisms.

► A mass-action model for IL6-mediated signaling via sequential binding is presented.
► Model shows an IL6 mechanism is sufficient to explain many in vitro experiments.
► Global sensitivity analysis (SA) indicates the most influential parameters are known.
► SA indicates inhibitor of sgp130 does not significantly affect differentiation.
► Soluble receptor pathway is more influential than the surface receptor pathway.