Topology of molecular networks offers signaling insusceptibility to temperature and ionic strength changes

The equilibrium constants of chemical reactions fundamentally depend on temperature, posing challenges for living systems. However, many conformer organisms do not maintain stable internal temperature. This raises the question: can molecular signaling pathways inherently resist temperature susceptibility? Molecular commutation is a recently discovered, fundamentally distinct mechanism for biological information processing and storage that underlies highly complex signal processing and computation using only molecular interactions governed by the law of mass action. Here we show that molecular commutation enables biological information processing networks to become temperature independent through compensatory reactions (i.e., network topology). Using complex logic gates, receptor-activator networks, and signaling systems with non-linear, non-monotonic functions (e.g., x 2 , x 3 ), we show that topological compensation preserves signaling function across temperatures up to 0.1–50 °C, despite dissociation constant changes of up to nine orders of magnitude. This mechanism also stabilizes systems against dramatic ionic strength shifts (e.g., Na + from 0.1–1 M). Thus, topological compensation is a unique homeostasis mechanism that may be used by delicate biological systems of arbitrarily high complexity. Graphical abstract