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Published on: October 5, 2012
Bistability in apoptosis by receptor clustering.
Kenneth L Ho1, Heather A Harrington
1Courant Institute of Mathematical Sciences and Program in Computational Biology, New York University, New York, New York, USA. ho@courant.nyu.edu
Plos Computational Biology
|October 27, 2010
Summary
Mathematical modeling reveals how Fas receptor clustering creates bistability, enabling cells to act as robust life/death switches. This receptor-ligand dynamics model explains cell fate decisions independent of downstream signaling.
Area of Science:
- Cell Biology
- Mathematical Biology
- Biophysics
Background:
- Apoptosis is a regulated cell death process crucial for physiology.
- The Fas death receptor and its ligand FasL are key in extrinsic apoptosis.
- Fas receptor oligomerization forms the death-inducing signaling complex.
Purpose of the Study:
- To propose a mathematical model for Fas ligand-receptor dynamics.
- To investigate how FasL-induced clustering leads to signaling platforms.
- To explain observed bistability and robustness in cell death decisions.
Main Methods:
- Developed a mathematical model of death ligand-receptor interactions.
- Analyzed receptor clustering and proximity-induced interactions.
- Investigated the role of FasL trimerism and receptor concentration.
Main Results:
- The model demonstrates hysteresis, leading to upstream bistability and robustness.
- Bistability depends on FasL trimerism at low receptor concentrations.
- Irreversible bistability, signifying committed cell death, emerges at high concentrations.
Conclusions:
- The model provides a unified theory for Fas-mediated apoptosis bistability.
- Fas receptor clustering acts as a mechanism for cell fate decision-making.
- Cells can function as bistable life/death switches via death receptor dynamics.
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