  Biophysical models are often populated by a large number of input parameters
that are difficult to predict or measure experimentally. The validity and
robustness of a given model can be evaluated by a sensitivity test to its input
parameters. In this study, we performed local (based on a Taylor-like method)
and global sensitivity (based on Monte Carlo filtering techniques) analyses of
a previously derived PAR1-mediated activation model of endothelial cells. This
activation model previously demonstrated that peptide-activated PAR1 has a
different receptor/G-protein binding affinity that favors Galpha_q activation
over Galpha_12/13 by approximately 800-fold. Interestingly, the present study
shows that the parameter regulating the binding rate of activated PAR1 to
Galpha_12/13 is indeed important to obtain the expected RhoGTP response.
Moreover, we show that the parameters representing the rate of PAR1
deactivation and the rate of PAR1 binding to G_q, are the most important
parameters in the system. Finally, we illustrate that the kinetic model
considered in this study is robust and we provide complementary insights into
the biological meaning and importance of its kinetic parameters.
