PT - JOURNAL ARTICLE AU - Zand, Armin M. AU - Gupta, Ankit AU - Khammash, Mustafa TI - Cascaded Antithetic Integral Feedback for Enhanced Stability and Performance AID - 10.1101/2024.07.31.605983 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.07.31.605983 4099 - http://biorxiv.org/content/early/2024/10/29/2024.07.31.605983.short 4100 - http://biorxiv.org/content/early/2024/10/29/2024.07.31.605983.full AB - Precise intracellular regulation and robust perfect adaptation can be achieved using biomolecular integral controllers and it holds enormous potential for synthetic biology applications. In this letter, we consider the cascaded implementation of a class of such integrator motifs. Our cascaded integrators underpin proportional-integral-derivative (PID) control structures, which we leverage to suggest ways to improve dynamic performance. Moreover, we demonstrate how our cascaded strategy can be harnessed to enhance robust stability in a class of uncertain reaction networks. We also discuss the genetic implementation of our controllers and the natural occurrence of their cascaded sequestration pairs in bacterial pathogens.Competing Interest StatementThe authors have declared no competing interest.