Computational modeling of signaling networks for eukaryotic chemosensing.

The task of developing and simulating computational models of signaling networks for eukaryotic chemosensing confronts the modeler with several challenges: (1) The stimuli that initiate the cellular responses one wishes to study are provided by extracellular concentration gradients. This means that the computational model must have a spatially resolved representation of extracellular molecular concentrations. (2) The intracellular responses consist of the generation of intracellular accumulations and/or translocations of signaling molecules, requiring spatially resolved computational representations of the simulated cells. (3) The signaling networks responsible for eukaryotic chemosensing comprise a multitude of components acting as receptors, adaptors, (lipid- and protein-) kinases (including GTPases), (lipid- and protein-) phosphatases, and molecule types used by others for membrane attachment. Models of such signaling networks may become quite complicated, unless one wishes to rely on abstract functional modules with certain input-output characteristics as modeling "shortcuts" replacing subnetworks of biological signaling molecules. In this chapter, we describe how modelers can use a modeling tool ("simmune") developed to facilitate the design and simulation of detailed computational models of signaling pathways (for eukaryotic chemosensing here), thereby avoiding the technical difficulties typically associated with building and simulating such quantitative models.