Sensitivity of signaling pathway dynamics to plasmid transfection and its consequences.

This paper deals with development of signaling pathways models and using plasmid-based experiments to support parameter estimation. We show that if cells transfected with plasmids are used in experiments, the models should include additional components that describe explicitly effects induced by plasmids. Otherwise, when the model is used to analyze responses of wild type, i.e. non-transfected cells, it may not capture their dynamics properly or even lead to false conclusions. In order to illustrate this, an original mathematical model of miRNA-mediated control of gene expression in the NFκB pathway is presented. The paper shows what artifacts might appear due to experimental procedures and how to develop the models in order to avoid pursuing these artifacts instead of real kinetics.