Characterization of tradeoffs in biomolecular signaling

Systems-level tradeoffs are fundamental in engineering, and recent work has highlighted an analogous role for them in biology. However, the extent of validity of these tradeoffs, especially for biomolecular systems, is generally unclear. Here, we address this issue for signaling tradeoffs that can constrain, for a fixed concentration of the signaling protein, a simultaneous enhancement of the gain and range of an amplifier or of the gain and threshold of a switch. We find that these gain-related tradeoffs persist in mathematical models of biomolecular reaction mechanisms that are at the core of large classes of signaling systems. Further, we find that these tradeoffs are also prevalent in the parametric functional forms commonly used to describe input–output curves in experimental analyses. Finally, we find that these tradeoffs can persist even in the presence of transcriptional feedback mechanisms that can change the concentration of the signaling protein. These results present a systematic characterization of these tradeoffs in biomolecular signaling systems.