Performance of Homeostatic Controller Motifs Dealing with Perturbations of Rapid Growth and Depletion

An
essential property of life is that cells and organisms have
the ability to protect themselves against external disturbances/attacks
by using homeostatic mechanisms. These defending mechanisms are based
on negative feedback regulation and often contain additional features,
such as integral control, where the integrated error between a controlled
variable and its set-point is used to achieve homeostasis. Although
the concept of integral control has its origin in industrial processes,
recent findings suggest that biological systems are also capable of
showing integral control. We recently described a basic set of negative
feedback structures (controller motifs) where robust homeostasis is
achieved against different but constant perturbations. As many perturbations
in biology, such as infections, increase rapidly over time, we investigated
how the different controller motifs equipped with different implementations
of integral control perform in relation to rapidly changing perturbations,
including exponential and hyperbolic changes. The findings show that
the construction of an optimum biochemical controller design for time-dependent
perturbations requires a certain match between the structure of the
negative feedback loop, its signaling kinetics, and the kinetics of
how integral control is implemented within the negative feedback loop.