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Ligand-receptor promiscuity enables cellular addressing.

Christina J Su¹, Arvind Murugan², James M Linton¹

¹Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

|April 14, 2022

Summary

Molecular promiscuity in cell signaling allows a few ligands to precisely address many cell types through combinations. This combinatorial approach enhances cellular addressing capabilities, even with noisy receptor expression.

Keywords:

BMP bone morphogenetic protein cell-type specificity combinatorial signaling communication systems information theory ligand-receptor interactions promiscuity signal processing signaling pathways

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Area of Science:

Cellular biology
Systems biology
Biochemistry

Background:

Multicellular organisms rely on secreted ligands to activate specific cell populations for crucial processes like cell fate decisions.
Complex cell-cell communication pathways often involve promiscuously interacting ligands and receptors, raising questions about achieving signaling specificity.

Purpose of the Study:

To investigate how signaling specificity can emerge from molecular promiscuity in ligand-receptor interactions.
To develop a mathematical framework for understanding cellular addressing mechanisms.

Main Methods:

Developed a general mathematical modeling framework.
Focused the model on the bone morphogenetic protein (BMP) pathway architecture.
Analyzed ligand-receptor interaction dynamics and cell type definition by receptor expression profiles.

Main Results:

Promiscuous ligand-receptor systems enable a small number of ligands, through combinations, to address a larger number of cell types.
Combinatorial addressing is more effective than one-to-one signaling architectures.
This addressing capability is robust to noise, increases with receptor variants, and depends on specific biochemical parameters.

Conclusions:

Ligand combinations provide a powerful mechanism for achieving cellular addressing specificity despite molecular promiscuity.
Identified key design principles for combinatorial cellular addressing in biological systems.