Figure 1. Simplified schematic representation of the complement system and reaction network diagram of the mathematical model.

(A) The complement cascade is triggered when CRP or L-ficolin is recruited to the bacterial surface by binding to ligand PC (classical pathway) or GlcNAc (lectin pathway). Under inflammation condition, CRP and ficolin interact with each other and induce amplification pathways. The activated CRP and L-ficolin on the surface interacts with C1 and MASP-2 respectively and leads to the formation of the C3 convertase (C4bC2a), which cleaves C3 to C3b and C3a. Deposition of C3b initiates the opsonization, phagocytosis, and lysis. C4BP regulates the activation of complement pathways by: (a) binding to CRP, (b) accelerating the decay of the C4bC2a, (c) binding to C4b, and (d) preventing the assembly of C4bC2a (red bars). Solid arrows and dotted arrows indicate protein conversions and enzymatic reactions, respectively. (B) Complexes are denoted by the names of their components, separated by a “:”. Single-headed solid arrows characterize irreversible reactions and double-headed arrows characterize reversible reactions. Dotted arrows represent enzymatic reactions. The kinetic equations of individual reactions are presented in the supplementary material. The reactions with high global sensitivities are labeled in red.