Table 4.

Modifications of the reduced Neumann’s model to reproduce the experimental data by Bentele et al

Step	Changed parameters and concentrations	Initial values, modifications	Reason	Ranges and initial values of fitting
1	CD95R:FADD	91.266 nM, increase	Case: anti-CD95 = 5 μg/ml Procaspase-8 is cleaved in about 30 minutes. This is possible only if DISC concentration reaches a level sufficient to accelerate the reaction nr2.	[102, 103], 442.821, Bentele et al.
2	procaspase-8	64.477 nM, increase	Case: anti-CD95 = 5 μg/ml The concentration of caspase-8 should reach its maxim value in about 20 minutes.	[102, 103], 442.821, Bentele et al.
3	FLIPS	5.084 nM, increase	Case: anti-CD95 = 200 ng/ml As mentioned in Table 2, activation of caspase-8 is mainly caused by caspase-3 and, therefore, is delayed approximately for 30 minutes. Since reactions nr2 and nr5 have the same rates, we cannot observe the delay, but when we reduce the rate of nr5, we can. The latter is achieved by upregulation of the DISC:pro8 complex inhibition.	[101, 102], 65.021, Bentele et al.
4	k10	0.121 nM-1min-1, decrease by an order of magnitude	Case: anti-CD95 = 200 ng/ml Preventing a rapid growth of caspase-8 concentration.	0.012
5	procaspase-3	1.443 nM, refitting	Case: anti-CD95 = 5 μg/ml Improving approximation of the experimental data by Bentele et al.	[100, 101], 1.443, Neumann et al.
6	Bid, procaspase-9	5.003 nM, 2.909 nM, replacement by Bentele’s values	Case: anti-CD95 = 200 ng/ml Reproducing the experimental dynamics of procaspase-9.	231.760 (Bid), 245.101 (pro-9), Bentele et al.