Multiscale Granuloma Simulations

an on-line supplement for

Multiscale computational modeling reveals a critical role for TNF-α receptor 1 dynamics in tuberculosis granuloma formation

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Fallahi-Sichani, M, El-Kebir, M, Marino, S, Kirschner, D*, Linderman, J. Multi-scale computational modeling reveals a critical role for TNF-α receptor 1 dynamics in tuberculosis granuloma formation. Journal of Immunology, 2011, March 15, vol. 186, no. 6, pp 3472-3483 (corresponding author)., DOI: 10.4049/jimmunol.1003299, PMID: 21321109, PMCID: 3127549






Supporting Text: Description of modeling methods
Supplementary Table S1: TNF-independent and cellular/tissue scale (ABM) parameters, definitions and estimated values
Supplementary Table S2: Molecular/single-cell scale TNF/TNFR parameters, definitions and values
Supplementary Table S3: Definition of reaction species, reactions describing TNF/TNFR processes and their rates
Supplementary Table S4: Differential equations describing TNF/TNFR processes
Supplementary Table S5: Linking parameters used to calculate the probability of TNF-induced cell responses, definitions and estimated values
Supplementary Table S6: LHS sensitivity analysis results for the effect of TNF-independent and cellular scale parameters on model outputs at day 200 post-infection
Supplementary Table S7: LHS sensitivity analysis results for the effect of TNF/TNFR-associated molecular and linking parameters on model outputs at day 200 post-infection






Movie 1

Movie 2
Control of Mtb infection within a
well-circumscribed granuloma

Clearance of Mtb

Movie 3

Movie 4
Uncontrolled growth of Mtb due to TNF deletion

Uncontrolled growth of Mtb due to IFN-&gamma deletion

Movie 5

Movie 6
Clearance of Mtb with extensive inflammation
at very slow rates of TNFR1 internalization

Clearance of Mtb at slow rates of
TNFR1 internalization

Movie 7

Movie 8
Containment of Mtb within the granuloma at
physiological rate of TNFR1 internalization

Uncontrolled growth of Mtb at rapid
rates of TNFR1 internalization



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