Signaling Architectures that Transmit Unidirectional Information Despite Retroactivity

Area of Science:

• Systems Biology
• Biophysics
• Biochemical Engineering

Background:

• Signaling pathways transmit information but face retroactivity, where downstream interactions impede unidirectional flow.
• The architecture of signaling pathways is crucial for overcoming retroactivity and ensuring signal fidelity.

Purpose of the Study:

• To develop a general mathematical procedure to analyze signaling pathway architectures for unidirectional signal transmission.
• To identify specific signaling architectures that can overcome retroactivity and enable one-way information flow.

Main Methods:

• Mathematical analysis of signaling pathway topologies.
• Evaluation of unidirectional signal transmission capabilities across various architectures under parameter tuning.

Main Results:

• Single-stage kinase-based phosphorylation and phosphotransfer systems exhibit a trade-off hindering retroactivity mitigation.
• Cascades of kinase-based systems effectively overcome this trade-off, enabling unidirectional signaling.
• Substrate-based phosphorylation cycles and phosphotransfer systems, even when cascaded, fail to mitigate retroactivity.

Conclusions:

• Specific signaling pathway topologies, particularly kinase-based cascades, are essential for achieving unidirectional information transmission.
• These findings reveal modular biological processes and provide a library of devices for synthetic biology circuit design.