Energy dependence of signalling dynamics and robustness in bacterial two component systems
One of the best known ways bacteria cells understand and respond to the environment are through Two-Component Systems (TCS). These signalling systems are highly diverse in function and can detect a range of physical stimuli including molecular concentrations and temperature, with a range of responses including chemotaxis and anaerobic energy production. TCS exhibit a range of different molecular structures and energy costs, and multiple types co-exist in the same cell. TCSs that incur relatively high energy cost are abundant in biology, despite strong evolutionary pressure to efficiently spend energy. We are motivated to discern what benefits, if any, the more energetically expensive variants had for a cell. We seek to answer this question by modelling energy flow through two variants of TCS. This was accomplished using bond graphs, a physics-based modelling framework that accurately models energy transfer through different physical domains. Our analysis demonstrates that energy availability can affect a cells signal sensitivity, noise filtering effectiveness, and the stimulus level where cell response is maximal. We also found that these properties are determined not by the molecular parameters themselves, but the reaction rate parameters that govern the reaction systems as a whole. This suggests possible connections between the molecular structure and evolutionary purpose of any two-component system. This opens the door to new synthetic circuit design in systems biology, and we propose new hypotheses about this link between structure and purpose that could be experimentally verified. Author summaryTwo-component systems are the main way many bacteria sense and respond to their environment. They exist in such well-studied bacteria as E. coli where they have been shown to detect a range of stimuli including nutrients, temperature, acidity, and pressure. Two-component systems are ubiquitous in bacteria yet have a deceptively simple structure. Knowing how they operate and the purpose of variations in signalling structure is helpful to our understanding of cellular biology and the design of synthetic biological circuits. Critical unanswered questions remain about the energy usage and functional benefits of these systems. We sought to improve our understanding of two-component systems by applying a physics-based modelling framework. We found that tracking energy flow through the cell reveals new energy-dependent behaviour in signalling sensitivity, noise filtering, and maximal cell response. We also found that these properties are not strictly dependent on the molecular properties themselves, but from the configuration of the reaction system as a whole.