Related Experiment Video
Updated: Mar 17, 2026

Flow Cytometric Analysis of Apoptotic Biomarkers in Actinomycin D-Treated SiHa Cervical Cancer Cells
Published on: August 26, 2021
Theoretical Analysis of Fas Ligand-Induced Apoptosis with an Ordinary Differential Equation Model
Zhimin Shi1, Yan Li1, Zhihai Liu1
1State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. China tel: 86-21-54925128.
Abstract:
Upon the treatment of Fas ligand, different types of cells exhibit different apoptotic mechanisms, which are determined by a complex network of biological pathways. In order to derive a quantitative interpretation of the cell sensitivity and apoptosis pathways, we have developed an ordinary differential equation model. Our model is intended to include all of the known major components in apoptosis pathways mediated by Fas receptor. It is composed of 29 equations using a total of 49 rate constants and 13 protein concentrations. All parameters used in our model were derived through nonlinear fitting to experimentally measured concentrations of four selected proteins in Jurkat T-cells, including caspase-3, caspase-8, caspase-9, and Bid. Our model is able to correctly interpret the role of kinetic parameters and protein concentrations in cell sensitivity to FasL. It reveals the possible reasons for the transition between type-I and type-II pathways and also provides some interesting predictions, such as the more decisive role of Fas over Bax in apoptosis pathway and a possible feedback mechanism between type-I and type-II pathways. But our model failed in predicting FasL-induced apoptotic mechanism of NCI-60 cells from their gene-expression levels. Limitations in our model are also discussed.
Insights
This study develops a mathematical model to quantitatively interpret cell sensitivity and apoptosis pathways. The model reveals key factors in Fas ligand-induced cell death and predicts pathway transitions.
Area of Science:
- Cellular biology
- Systems biology
- Mathematical modeling
Background:
- Fas ligand (FasL) triggers diverse apoptotic mechanisms across cell types.
- Apoptosis pathways are regulated by complex biological networks.
- Quantitative interpretation of these pathways is crucial for understanding cell sensitivity.
Purpose of the Study:
- To develop a quantitative ordinary differential equation (ODE) model of Fas receptor-mediated apoptosis.
- To analyze the role of kinetic parameters and protein concentrations in cell sensitivity to FasL.
- To investigate the transition between type-I and type-II apoptotic pathways.
Main Methods:
- Developed a 29-equation ODE model incorporating major apoptosis pathway components.
- Calibrated model parameters using nonlinear fitting to experimental protein concentrations (caspase-3, -8, -9, Bid) in Jurkat T-cells.
- Analyzed model predictions regarding FasL-induced apoptosis.
Main Results:
- The model accurately interprets kinetic parameters and protein concentrations influencing cell sensitivity to FasL.
- Identified potential reasons for the switch between type-I and type-II apoptosis pathways.
- Predicted a more significant role for Fas compared to Bax and suggested a feedback mechanism between pathway types.
Conclusions:
- The ODE model provides quantitative insights into Fas-mediated apoptosis.
- The model highlights the critical influence of specific proteins and parameters on cell death.
- Further refinement is needed for predicting apoptosis in diverse cell lines like NCI-60 cells based on gene expression.
Related Concept Videos
The Extrinsic Apoptotic Pathway
Modeling with Differential Equations
The Intrinsic Apoptotic Pathway
Caspases
Apoptosis

