MAYORGA Luis Segundo
congresos y reuniones científicas
Reproducing transport along the endocytic and secretory pathways using an agent-based modeling strategy.
RICCI, A; FLORES, G; MAYORGA, LS
Simposio; II International Symposium Translational Medicine.; 2019
UNCuyo, UBA, Freiburg University Germany
Intracellular transport is a key process in eukaryotic cells. Substances need to be transported in membrane-bound organelles along the endocytic and secretory pathways. At present, hundreds of factors that are necessary for this process have been identified. However, the way intracellular transport is accomplished is far from being deciphered. Cargo transport along the endocytic and secretory routes strongly depends on fusion and fission events. We have developed a computational model that accurately reproduces experimental transport data of soluble and membrane-associated cargoes along the endocytic route. This agent-based modeling strategy is based on iterative fusion and fission events. In the model, we included five membrane domains corresponding to early, late, sorting, and recycling endosomes and the trans Golgi network (TGN). Fusion causes the mixing of membrane domains and luminal content of the interacting organelles. During fission, the membrane domains can be sorted out, restoring the identity of each organelle. Soluble cargos are distributed according to the volume of the divided structures, and membrane cargoes according to the area. This even distribution can be affected by the size of the soluble cargo and by the affinity of membrane-bound cargoes for specific membrane domains. The mechanism of trafficking of macromolecules along the Golgi apparatus is still controversial. Different experimental observations indicate that a pure cistern maturation mechanism or vesicle-based transport are unlikely. We found that iterative fusion/fission events accurately reproduce anterograde and retrograde transport in a set of organelles simulating a complete Golgi apparatus. The model captures the highly dynamic nature of cell compartments that fuse and divide, creating different conditions for each organelle. We expect that this modeling strategy will be useful to understand the logic underlying the organization and function of the endomembrane system.