Automatic method to combine three model layers of the cell. C. Moulin1, E. Bigan2, J. da Veiga Moreira2, L. Schwartz3, M. Jolicoeur4, S. Peres1,5 1. LRI, Gif-sur-Yvette, France 2. LIX, Palaiseau, France 3. AHP, Paris, France 4. Polytechnique, Montréal, Canada 5. MaIAGE INRA, Jouy-en-Josas, France Motivation Metabolism is an important part of the cell proliferation. The changes between catabolism and anabolism are controled by intracellular oscillators : NAD(H), NADP(H), pH, ATP. To better understand the differencies between cancer and normal cells, those oscillators were measured in cancer and normal cells extracted from human colon. A Models ● Metabolism Central Carbon Metabolism ● Electrochemistry ● pH model C B ➔ ➔ Geometry Imposed as time function Deducted from metabolism dV =V growth∗V dt dA K s = ∗A∗[ PALM ] dt N me ● Results Model ➔ Generic program for coupling models Input : metabolic model, electrochemical model and parameters Standardize the units Adjust models to connect them in pooling some metabolites (ATP, ADP, H ...) ➔ ➔ ● Output : differential equations system and curves Imposed Deducted Connect to geometry ➔ Dilution ➔ Surface reaction vs inner cell reaction Perspectives ● Change the geometry pattern : be more specific with the shape – add information about cell cycle ● Be more specific with the enzymes : add their pH-sensibility – concentration not constant through cell cycle ● Add cell compartment, especially the mitochondrion for its link to cellular respiration and the Warburg effect References A. M. Abolhassani, J. Da Veiga Moreira, E. Bigan, S. Peres, L. Pauleve, M. Levy Nogueira, J.-M. Steyaert, L. Schwartz, The redox status of cancer cells supports mechanisms behind the Warburg effect B. J. Robitaille, J. Chen, M. Jolicoeur, (2015) A Single Dynamic Metabolic Model Can Describe mAb Producing CHO Cell Batch and FedBatch Cultures on Different Culture Media. PLoS ONE 10(9) : e0136815. doi :10.1371/journal.pone.0136815 C. Y. Bouret, M. Argentina, L. Counillon (2014) Capturing Intracellular pH Dynamics by Coupling Its Molecular Mechanisms within a Fully Tractable Mathematical Model. PLoS ONE 9(1) : e85449. doi :10.1371/journal.pone.0085449 Contact : [email protected],fr