# Cell-to-Cell stochastic fluctuations in apoptotic signaling can decide between life and death

**Authors:** S. Raychaudhuri, E. Willgohs, T. Nguyen, E. M. Khan, T. Goldkorn  
**arXiv:** [0707.1569](https://arxiv.org/abs/0707.1569)  
**Date:** 2007-07-11  
**Summary page:** https://www.summarizepaper.com/en/paper/0707.1569v1/

## Key points

- Apoptosis is a crucial cellular process that maintains the balance between life and death in cells.
- The molecular mechanism of apoptotic signaling and how these two pathways are differentially activated under distinct apoptotic stimuli is poorly understood.
- A Monte Carlo-based stochastic simulation model was developed to characterize distinct signaling behaviors in the two major pathways of apoptotic signaling using a novel probability distribution-based approach.
- For weak death signals such as low levels of death ligand Fas (CD95) binding or under stress conditions, the type 2 mitochondrial pathway dominates apoptotic signaling.
- Signaling in the type 2 pathway is stochastic, where the population average over many cells does not capture the cell-to-cell fluctuations in the time course (~1 - 10 hours) of downstream caspase-3 activation.
- The probability distribution of caspase-3 activation for the mitochondrial pathway shows a distinct bimodal behavior that can be used to characterize stochastic signaling in type 2 apoptosis.
- Stochastic fluctuations in apoptosis signaling happen even in the presence of large numbers of signaling molecules, which may be an adaptive mechanism for allowing a competing survival signal to win over a weak death trigger before making critical cell fate decisions and thus minimizing pathologies' risk.

## Summary

Apoptosis, or programmed cell death, is a crucial cellular process that maintains the balance between life and death in cells. However, the precise molecular mechanism of apoptotic signaling and how these two pathways are differentially activated under distinct apoptotic stimuli is poorly understood. To address this issue, a team of researchers developed a Monte Carlo-based stochastic simulation model that characterizes distinct signaling behaviors in the two major pathways of apoptotic signaling using a novel probability distribution-based approach. Their findings showed that for weak death signals such as low levels of death ligand Fas (CD95) binding or under stress conditions, the type 2 mitochondrial pathway dominates apoptotic signaling. Interestingly, they also found that signaling in the type 2 pathway is stochastic; where the population average over many cells does not capture the cell-to-cell fluctuations in the time course (~1 - 10 hours) of downstream caspase-3 activation. On the contrary, they discovered that the probability distribution of caspase-3 activation for the mitochondrial pathway shows a distinct bimodal behavior that can be used to characterize stochastic signaling in type 2 apoptosis. Furthermore, their results revealed that such stochastic fluctuations in apoptosis signaling happen even in the presence of large numbers of signaling molecules. In a fluctuating environment, this stochasticity may be an adaptive mechanism for allowing a competing survival signal to win over a weak death trigger before making critical cell fate decisions and thus minimizing pathologies' risk. In conclusion, this study sheds light on how cell-to-cell stochastic fluctuations in apoptotic signaling can decide between life and death. The authors' findings provide valuable insights into understanding apoptosis's molecular mechanisms and its role in maintaining cellular homeostasis.