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Ultrasensitive responses and specificity in cell signaling
Seth Haney1, Lee Bardwell, Qing Nie
1Department of Mathematics, University of California at Irvine, Irvine, CA 92697, USA.
BMC Systems Biology
|August 26, 2010
Summary
Cell signaling pathways use ultrasensitivity to achieve specificity, but input fidelity remains challenging. Scaffolding mechanisms significantly enhance both specificity and fidelity in these networks.
Area of Science:
- Systems Biology
- Biophysics
- Biochemistry
Background:
- Cell signaling pathways transmit signals with high accuracy despite potential crosstalk.
- Biological systems employ network-level mechanisms to insulate pathways and maintain signal integrity.
- Ultrasensitive (switch-like) responses are common in signaling pathways, but their role in specificity is underexplored.
Purpose of the Study:
- Investigate if interconnected signaling pathways can achieve output specificity and input fidelity.
- Examine the role of ultrasensitivity in attaining these performance objectives.
- Analyze the impact of insulating mechanisms on pathway specificity and fidelity.
Main Methods:
- Mathematical modeling of two interconnected signaling pathways sharing an intermediate component.
- Analysis of pathway behavior under different activation conditions (hyperbolic, ultrasensitive).
- Evaluation of specificity and fidelity in the presence and absence of insulating mechanisms (cross-pathway inhibition, combinatorial signaling, scaffolding/compartmentalization).
Main Results:
- Mutual specificity is achievable in hyperbolic or ultrasensitive pathways without insulation.
- Mutual input fidelity is unattainable at steady-state, even with ultrasensitive pathways.
- Ultrasensitivity enhances specificity and fidelity when combined with insulating mechanisms, particularly scaffolding/compartmentalization.
Conclusions:
- Achieving high signaling specificity faces inherent constraints, influencing the evolution of signaling networks.
- Input fidelity is more challenging to achieve than output specificity.
- Ultrasensitivity significantly boosts the effectiveness of insulating mechanisms, especially scaffolding, for improving network specificity and fidelity.
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