Developing a platform that combines agent-based and differential equations approaches to model intracellular transport

FLORES, G; MAYORGA, LS

Buenos Aires

Congreso; Reunión Conjunta Sociedades Biociencias; 2017

SAIB

Abstract: Intracellular transport is a key process in eukaryotic cells.Substances need to be transported in membrane-bound organellesalong the endocytic and secretory pathways. Transport inside thecell is required for secretion of hormones and neurotransmitters, forantigen presentation and microbe defense and many other fundamentalcell functions. At present, hundreds of factors that are necessaryfor this process have been identified. However, the way intracellulartransport is accomplished is far from being deciphered. Wehave developed a combined agent (ABM) - and differential equation(ODE) -based model of intracellular transport. The resulting modelhas the flexibility to accommodate the dynamic nature of intracellularstructures that move, interact, fuse and divide, and the associatedbiochemical reactions. At present the model include five organellesidentified by five different Rab domains, that correspond to early,sorting, recycling and late endosomes, plus a secretory compartmentcorresponding to the trans Golgi network. The behavior ofthe organelles is specified in ABM, whereas Rabs concentration iscontrolled by ODEs programmed in COPASI. Antigen digestion andcross presentation is also modelled in COPASI. In the simulation,the organelles are stable for more than 50.000 steps, correspondingto times of about 20 minutes. Internalized soluble proteins arecorrectly directed to degradative organelles and membrane boundproteins are able to recycle to the cell surface. The expectation isthat the model will be a useful tool to understand the dynamic natureof the intracellular organelles that work as platforms to control manykey functions of the cell biology.