Experimental evidence for constraints in amplitude-timescale co-variation of a biomolecular pulse generating circuit design

Abstract

Understanding constraints on the functional properties of biomolecular circuit dynamics, such as the possible variations of amplitude and timescale of a pulse, is an important part of biomolecular circuit design. While the amplitude-timescale co-variations of the pulse in an incoherent feedforward loop have been investigated computationally using mathematical models, experimental support for any such constraints is relatively unclear. Here, the authors address this using experimental measurement of an existing pulse generating incoherent feedforward loop circuit realisation in the context of a standard mathematical model. They characterise the trends of co-variation in the pulse amplitude and rise time computationally by randomly exploring the parameter space. They experimentally measured the co-variation by varying inducers and found that larger amplitude pulses have a slower rise time. They discuss the gap between the experimental measurements and predictions of the standard model, highlighting model additions and other biological factors that might bridge the gap.