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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 : moulin@lri,fr


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