Abstract

BackgroundAdaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts. Much of the current understanding of adaptation in network modules/motifs is based on their response to simple stimuli. Recently, there have also been studies of adaptation in dynamic stimuli. However a broader synthesis of how different circuits of adaptation function, and which circuits enable a broader adaptive behaviour in classes of more complex and spatial stimuli is largely missing.ResultsWe study the response of a variety of adaptive circuits to time-varying stimuli such as ramps, periodic stimuli and static and dynamic spatial stimuli. We find that a variety of responses can be seen in ramp stimuli, making this a basis for discriminating between even similar circuits. We also find that a number of circuits adapt exactly to ramp stimuli, and dissect these circuits to pinpoint what characteristics (architecture, feedback, biochemical aspects, information processing ingredients) allow for this. These circuits include incoherent feedforward motifs, inflow-outflow motifs and transcritical circuits. We find that changes in location in such circuits where a signal acts can result in non-adaptive behaviour in ramps, even though the location was associated with exact adaptation in step stimuli. We also demonstrate that certain augmentations of basic inflow-outflow motifs can alter the behaviour of the circuit from exact adaptation to non-adaptive behaviour. When subject to periodic stimuli, some circuits (inflow-outflow motifs and transcritical circuits) are able to maintain an average output independent of the characteristics of the input. We build on this to examine the response of adaptive circuits to static and dynamic spatial stimuli. We demonstrate how certain circuits can exhibit a graded response in spatial static stimuli with an exact maintenance of the spatial mean-value. Distinct features which emerge from the consideration of dynamic spatial stimuli are also discussed. Finally, we also build on these results to show how different circuits which show any combination of presence or absence of exact adaptation in ramps, exact mainenance of time average output in periodic stimuli and exact maintenance of spatial average of output in static spatial stimuli may be realized.ConclusionsBy studying a range of network circuits/motifs on one hand and a range of stimuli on the other, we isolate characteristics of these circuits (structural) which enable different degrees of exact adaptive and homeostatic behaviour in such stimuli, how they may be combined, and also identify cases associated with non-homeostatic behaviour. We also reveal constraints associated with locations where signals may act to enable homeostatic behaviour and constraints associated with augmentations of circuits. This consideration of multiple experimentally/naturally relevant stimuli along with circuits of adaptation of relevance in natural and engineered biology, provides a platform for deepening our understanding of adaptive and homeostatic behaviour in natural systems, bridging the gap between models of adaptation and experiments and in engineering homeostatic synthetic circuits.

Highlights

  • Adaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts

  • For instance models KR09 and KR11 are models of an incoherent feedforward adaptive motif developed to explain adaptation in Dictyostelium, and an expansion of that model to incorporate saturation

  • It is clear that dynamic stimuli/environments may be routinely encountered in cellular contexts, and any in-depth understanding of the role of adaptation and homeostasis in cellular information processing has to properly account for this

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Summary

Introduction

Adaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts. Cellular systems employ a number of distinct and characteristic nonlinear information processing modules, such as monostable switches, bistable switches and oscillators. Each of these modules plays critical roles in cells, and such modules has been a focal point in a number of cellular contexts [1,2,3,4,5]. In the case of Dictyostelium, adaptation to spatially uniform stimuli is seen alongside non-adaptive behaviour in spatial gradients In both these cases, it appears that adaptation has been incorporated, through evolution, into signal transduction to realize specific capabilities for cells. Homeostasis in cellular systems in response to different changes in the environment, is associated with adaptive behaviour of this kind, an example being iron homeostasis in bacteria [18,19,20,21,22,23,24]

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