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Updated: Jul 31, 2026
08:27
Use of a Caspase Multiplexing Assay to Determine Apoptosis in a Hypothalamic Cell Model
Published on: April 16, 2014
Stochastic modelling of apoptosis kinetics
D A Fennell1, A Pallaska, M Corbo
1Functional Genomics Unit, Barts and the London School of Medicine and Dentistry, London, UK. d.fennell@qub.ac.uk
Summary
This study introduces a kinetic model to quantify mitochondrial dysfunction, aiding in the assessment of apoptosis sensitivity. The method uses cumulative frequency distributions to estimate cell population responses to apoptotic stimuli.
Area of Science:
- Cell Biology
- Biophysics
- Quantitative Biology
Background:
- Assessing mitochondrial dysfunction is crucial for understanding apoptosis sensitivity.
- Current methods may lack robust quantitative estimation for population-level analysis.
- Novel agents and genetic/pharmacological manipulations require precise sensitivity measurements.
Purpose of the Study:
- To develop a robust quantitative method for estimating average whole cell mitochondrial dysfunction.
- To assess sensitivity to apoptotic stimuli using a novel kinetic modeling approach.
- To provide a tool for evaluating novel agents or genetic/pharmacological manipulations affecting apoptosis.
Main Methods:
- Mathematical modeling of mitochondrial membrane potential depolarization kinetics as a Bernoulli transition.
- Utilizing exponential distribution to derive median latency preceding depolarization.
- Fitting the kinetic model to in vitro single-cell data from kinetic flow cytometry using non-linear regression.
Main Results:
- A kinetic model was developed to describe mitochondrial membrane potential depolarization in cell populations.
- The model successfully fits single-cell resolution data from kinetic flow cytometry.
- Median latency preceding mitochondrial membrane potential dissipation can be derived.
Conclusions:
- Kinetic determination of cumulative frequency distributions offers a robust approach to estimate apoptosis sensitivity.
- This method is effective for assessing cell population responses over short time frames.
- The developed model provides a valuable tool for quantitative analysis of mitochondrial dysfunction and apoptosis.
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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
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