Modeling the Nonlinear Dynamics of Intracellular Signaling Networks

This protocol illustrates a pipeline for modeling the nonlinear behavior of intracellular signaling pathways. At fixed spatial points, nonlinear signaling dynamics are described by ordinary differential equations (ODEs). At constant parameters, these ODEs may have multiple attractors, such as multiple steady states or limit cycles. Standard optimization procedures fine-tune the parameters for the system trajectories localized within the basin of attraction of only one attractor, usually a stable steady state. The suggested protocol samples the parameter space and captures the overall dynamic behavior by analyzing the number and stability of steady states and the shapes of the assembly of nullclines, which are determined as projections of quasi-steady-state trajectories into different 2D spaces of system variables. Our pipeline allows identifying main qualitative features of the model behavior, perform bifurcation analysis, and determine the borders separating the different dynamical regimes within the assembly of 2D parametric planes. Partial differential equation (PDE) systems describing the nonlinear spatiotemporal behavior are derived by coupling fixed point dynamics with species diffusion.

Automated summary

This protocol outlines a process for modeling the nonlinear behavior of intracellular signaling pathways, utilizing methods such as sampling parameter space and analyzing steady state stability to capture overall dynamic behavior. The protocol allows identification of main qualitative features, bifurcation analysis, and determination of borders separating different dynamical regimes within 2D parametric planes.