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Ultrasensitive response motifs: basic amplifiers in molecular signalling networks.

Qiang Zhang¹, Sudin Bhattacharya, Melvin E Andersen

¹Center for Dose Response Modeling, Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA. qzhang@thehamner.org

|April 26, 2013

Summary

This review explores ultrasensitive response motifs (URMs) that amplify cellular signals. These key molecular circuits enable complex cell behaviors like fate determination and homeostasis.

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Area of Science:

Molecular Biology
Systems Biology
Biochemistry

Background:

Cellular responses rely on complex signal transduction and gene regulatory networks.
Network motifs are fundamental building blocks of these molecular signaling networks.

Purpose of the Study:

To review ultrasensitive response motifs (URMs) that amplify small input signal changes into larger output changes.
To discuss the kinetic mechanisms and applications of six common URMs in intracellular molecular networks.

Main Methods:

Literature review of ultrasensitive response motifs (URMs).
Analysis of kinetic mechanisms for signal amplification.
Discussion of URM combinations and their role in generating nonlinear dynamics.

Main Results:

Six types of URMs identified: positive cooperative binding, homo-multimerization, multistep signaling, molecular titration, zero-order covalent modification cycle, and positive feedback.
URMs exhibit sigmoid input-output relationships, steeper than Michaelis-Menten kinetics.
Combinations of URMs can create highly switch-like responses.

Conclusions:

URMs act as essential signal amplifiers in molecular circuits.
These motifs are crucial for generating complex nonlinear dynamics like multistability, adaptation, and oscillation.
The resulting dynamic properties govern higher-level cellular behaviors, including cell fate determination and homeostasis.