Stochastic modelling of apoptosis kinetics.
Robust quantitative estimation of average whole cell mitochondrial dysfunction is a useful tool for assessing sensitivity to apoptotic stimuli induced either by novel agents, or following manipulation of apoptotic threshold by pharmacological or functional genomics approaches. We have mathematically modelled the kinetics of whole cell mitochondrial membrane potential depolarisation within a population of cells as a Bernouli transition. An exponential distribution enables the median latency preceding mitochondrial membrane potential dissipation to be derived. The kinetic model can be fitted to in vitro single cell resolution data derived from kinetic flow cytometric studies by non-linear regression. We propose that kinetic determination of cumulative frequency distributions provides a useful approach for estimating apoptosis sensitivity across cell populations over short time-frames.
Fennell
D A
DA
Functional Genomics Unit, Barts and the London School of Medicine and Dentistry, London, UK. d.fennell@qub.ac.uk
Pallaska
A
A
Corbo
M
M
Cotter
F E
FE
D017209:Apoptosis; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D008928:Mitochondria / Q000473:pathology; D015233:Models, Statistical; D008962:Models, Theoretical; D013269:Stochastic Processes; D013997:Time Factors