Parameter-free methods distinguish Wnt pathway models and guide design of experiments
MacLean AL., Rosen Z., Byrne HM., Harrington HA.
Significance The canonical Wnt/β-catenin signaling pathway is important for essential cellular functions and is implicated in many diseases. We introduce a new mathematical model that focuses on β-catenin degradation and protein shuttling between cellular compartments. We compare our model to others and show that all fit to time-dependent experimental data. To evade this parameter problem, we use algebraic methods and characterize model features that are independent of the choice of parameter values. We find that multiple responses to Wnt are feasible under certain conditions for the new model, but not for the others; moreover, we provide dependencies between species (variables) that inform future experiments and model discrimination. We also highlight the wide applicability of these tools across problems in systems biology.