Robust perfect adaptation in bacterial chemotaxis through integral feedback control

TLDR

Integral feedback control ensures robust tracking of desired outputs and underlies adaptation, a process by which biological systems return to baseline despite persistent stimuli, as demonstrated by the robust precision of bacterial chemotaxis and suggested to support many homeostatic mechanisms. The study proposes that perfect adaptation’s robustness arises from integral feedback control in the bacterial chemotaxis network. The authors use control theory to show that integral control is structurally inherent in the Barkai–Leibler model and delineate its key assumptions. They conclude that integral control is necessary for robust perfect adaptation.

Abstract

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In biological systems, it is common for the response to an extracellular stimulus to return to its prestimulus value even in the continued presence of the signal—a process termed adaptation or desensitization. Barkai, Alon, Surette, and Leibler have provided both theoretical and experimental evidence that the precision of adaptation in bacterial chemotaxis is robust to dramatic changes in the levels and kinetic rate constants of the constituent proteins in this signaling network [Alon, U., Surette, M. G., Barkai, N. & Leibler, S. (1998) Nature (London) 397, 168–171]. Here we propose that the robustness of perfect adaptation is the result of this system possessing the property of integral feedback control. Using techniques from control and dynamical systems theory, we demonstrate that integral control is structurally inherent in the Barkai–Leibler model and identify and characterize the key assumptions of the model. Most importantly, we argue that integral control in some form is necessary for a robust implementation of perfect adaptation. More generally, integral control may underlie the robustness of many homeostatic mechanisms.