Dynamical compensation in physiological circuits. Issue 11 (8th November 2016) - Karin, Omer
Abstract: Biological systems can maintain constant steady‐state output despite variation in biochemical parameters, a property known as exact adaptation. Exact adaptation is achieved using integral feedback, an engineering strategy that ensures that the output of a system robustly tracks its desired value. However, it is unclear how physiological circuits also keep their output dynamics precise—including the amplitude and response time to a changing input. Such robustness is crucial for endocrine and neuronal homeostatic circuits because they need to provide a precise dynamic response in the face of wide variation in the physiological parameters of their target tissues; how such circuits compensate their dynamics for unavoidable natural fluctuations in parameters is unknown. Here, we present a design principle that provides the desired robustness, which we call dynamical compensation (DC). We present a class of circuits that show DC by means of a nonlinear feedback loop in which the regulated variable controls the functional mass of the controlling endocrine or neuronal tissue. This mechanism applies to the control of blood glucose by insulin and explains several experimental observations on insulin resistance. We provide evidence that this mechanism may also explain compensation and organ size control in other physiological circuits. Synopsis: Physiological circuits must keep their output dynamics precise despite wide variation in circuit parameters. We present a design principle for this robustness, find that it explains experimental observations on glucose homeostasis, and show that it may apply to other physiological circuits. Dynamical compensation (DC) is precise output dynamics despite variation in parameters. A design principle and sufficient conditions for DC is presented. Glucose regulation by beta‐cell functional mass has DC. Other physiological circuits have the hallmarks of DC. Abstract : Physiological circuits must keep their output dynamics precise despite wide variation in circuit parameters. We present a design principle for this robustness, find that it explains experimental observations on glucose homeostasis, and show that it may apply to other physiological circuits.