  An ubiquitous property of biological sensory systems is adaptation: a step
increase in stimulus triggers an initial change in a biochemical or
physiological response, followed by a more gradual relaxation toward a basal,
pre-stimulus level. Adaptation helps maintain essential variables within
acceptable bounds and allows organisms to readjust themselves to an optimum and
non-saturating sensitivity range when faced with a prolonged change in their
environment. Recently, it was shown theoretically and experimentally that many
adapting systems, both at the organism and single-cell level, enjoy a
remarkable additional feature: scale invariance, meaning that the initial,
transient behavior remains (approximately) the same even when the background
signal level is scaled. In this work, we set out to investigate under what
conditions a broadly used model of biochemical enzymatic networks will exhibit
scale-invariant behavior. An exhaustive computational study led us to discover
a new property of surprising simplicity and generality, uniform linearizations
with fast output (ULFO), whose validity we show is both necessary and
sufficient for scale invariance of enzymatic networks. Based on this study, we
go on to develop a mathematical explanation of how ULFO results in scale
invariance. Our work provides a surprisingly consistent, simple, and general
framework for understanding this phenomenon, and results in concrete
experimental predictions.
