Design and Implementation of a Biomolecular Concentration Tracker

As
a field, synthetic biology strives to engineer increasingly
complex artificial systems in living cells. Active feedback in closed
loop systems offers a dynamic and adaptive way to ensure constant
relative activity independent of intrinsic and extrinsic noise. In
this work, we use synthetic protein scaffolds as a modular and tunable
mechanism for concentration tracking through negative feedback. Input
to the circuit initiates scaffold production, leading to colocalization
of a two-component system and resulting in the production of an inhibitory
antiscaffold protein. Using a combination of modeling and experimental
work, we show that the biomolecular concentration tracker circuit
achieves dynamic protein concentration tracking in Escherichia
coli and that steady state outputs can be tuned.