Misc,
The Fas trimer hysteron model: bistability in apoptosis from receptor clustering
(2009)cite arxiv:0912.1548 Comment: 26 pages, 6 figures; supplementary information, 15 pages, 6 figures.
Abstract
Apoptosis is a highly regulated cell death mechanism involved in many
physiological processes. One of the key components of extrinsically activated
apoptosis is the death receptor Fas, which, on binding to its cognate ligand,
oligomerize to form the death-inducing signaling complex, a pivotal trigger of
apoptosis. Motivated by recent experimental data demonstrating the capacity of
Fas to self-stabilize in their signaling forms, we propose a mathematical model
of death ligand-receptor interaction that exhibits hysteresis. This provides an
upstream mechanism for bistability in apoptosis, which is seen to be a
consequence of biologically observed receptor trimerization. We analyze the
bistability thresholds of the model, which furthermore possesses robustness of
bistability, and provide a model assessment criterion using tools from
algebraic geometry. Our results strongly suggest a role for Fas and other death
receptors in generating robust threshold switching between coherent life and
death states. Discussion includes an analogy with ferromagnetism and the
generalization of self-stabilization to other apoptotic complexes such as the
apoptosome.
