In silico testing the fundamental mechanisms and logic of intracellular traffic

Abstract

Intracellular traffic is a central process in cellular physiology. Numerous macromolecules must be transported in the endocytic and exocytic pathways for the correct function of eukaryotic cells. However, the way by which macromolecules are transported between compartments is still a matter of intense debate. Our group has developed a simulation platform, based on a combination of agent-based modeling and ordinary differential equations, for processes that occur in dynamic organelles that merge, divide, and change position and shape, while altering their composition by complex networks of molecular interactions and chemical reactions. We have already described how this modeling strategy successfully reproduces transport in the endocytic pathway. Our next objective is to apply this modeling approach to the trafficking within the Golgi apparatus. It is worth mentioning that several hypotheses regarding this issue are still in conflict, despite the abundance of experimental results and the development of ingenious probes to assess transport. Interestingly, our modeling strategy is flexible enough to simulate all these hypotheses and test the agreement between the different models and experimental data. At present, we have successfully modeled the transport of small and large membrane-associated cargos using the “cisternal progression/maturation” hypothesis. We expect that the active dialogue between simulations and experimental results will foster our understanding of the logic underlying the transport mechanisms that efficiently sort a large number of macromolecules to their final destination inside and outside the cell.