2009/05/27 by Roberto Chignola, Chignola, Roberto, Marcello Farina +6
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Cell Behavior (q-bio.CB) #Cell death mechanisms and regulation #FOS: Biological sciences #Immune Response and Inflammation #Molecular Networks (q-bio.MN) #NF-κB Signaling Pathways #q-bio.CB #q-bio.MN
paper · pdf · doi:10.48550/arxiv.0905.4396
32 pages, 6 figures
openalex publication_date 2009/05/27 · arxiv created 2009/10/30 · arxiv updated 2009/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Tumor Necrosis Factor alpha (TNF) initiates a complex series of biochemical events in the cell upon binding to its type R1 receptor (TNF-R1). Recent experimental work has unravelled the molecular regulation of the recruitment of initial signaling complexes that lead either to cell survival or death. Survival signals are activated by direct binding of TNF to TNF-R1 at the cell membrane whereas apoptotic signals by endocytosed TNF/TNF-R1 complexes. Here we investigate these aspects by developing a quantitative mathematical model of TNF binding, internalization and intracellular signaling. Model outputs compare favorably with experimental data and allow to compute TNF-mediated cytotoxicity as observed in different cell systems. We extensively study the space of parameters to show that the model is structurally stable and robust over a broad range of parameter values. Thus, our model is suitable for implementation in multi-scale simulation programs that are presently under development to study the behavior of large tumor cell populations.