Enabling molecular signaling with temperature and ionic-strength independence or programmable dependence.

The equilibrium constants of chemical reactions fundamentally depend on temperature, posing challenges for living systems. However, many conformer organisms do not maintain a stable internal temperature. This raises the question: can molecular signaling pathways inherently resist temperature susceptibility? Molecular commutation is a recently discovered, fundamentally distinct mechanism of biological information processing and storage within reversible association/dissociation reactions. Here, we show that molecular commutation enables complex signaling systems that are independent of temperature and ionic strength and, even more generally, programmably dependent on these parameters. Using examples of various DNA logic gates, receptor-activator networks, and systems with complex input-output relationships (e.g., computed as algebraic functions), we demonstrate computationally that introducing compensatory reactions in these networks can render their signaling independent of temperature and ionic strength. We experimentally validate such independence for a case of a YES-logic gate. Finally, we computationally demonstrate networks with outputs that follow predefined functional forms of temperature and ionic strength (e.g., sin(T), where T is temperature). The presented intrinsic capabilities of affinity-based networks provide a remarkable homeostasis and signaling control mechanism that may be used by biological systems of arbitrarily high complexity.