Compact attractors of an antithetic integral feedback system have a simple structure

Since its introduction by Briat, Gupta and Khammash, the antithetic feedback controller design has attracted considerable attention in both theoretical and experimental systems biology. The case in which the plant is a two-dimensional linear system (making the closed-loop system a nonlinear four-dimensional system) has been analyzed in much detail. This system has a unique equilibrium but, depending on parameters, it may exhibit periodic orbits. An interesting open question is whether other dynamical behaviors, such as chaotic attractors, might be possible for some parameter choices. This note shows that, for any parameter choices, every bounded trajectory satisfies a Poincaré-Bendixson property. The analysis is based on the recently introduced notion of k-cooperative dynamical systems. It is shown that the model is a strongly 2-cooperative system, implying that the dynamics in the omega-limit set of any precompact solution is conjugate to the dynamics in a compact invariant subset of a two-dimensional Lipschitz dynamical system, thus precluding chaotic and other strange attractors.

[1]  Sandeep Krishna,et al.  Oscillation patterns in negative feedback loops , 2006, Proceedings of the National Academy of Sciences.

[2]  L. Sanchez,et al.  Cones of rank 2 and the Poincaré–Bendixson property for a new class of monotone systems , 2009 .

[3]  Michael Margaliot,et al.  Dynamical Systems With a Cyclic Sign Variation Diminishing Property , 2018, IEEE Transactions on Automatic Control.

[4]  J. Smillie Competitive and Cooperative Tridiagonal Systems of Differential Equations , 1984 .

[5]  Ankit Gupta,et al.  Antithetic Integral Feedback Ensures Robust Perfect Adaptation in Noisy Biomolecular Networks. , 2014, Cell systems.

[6]  Fulvio Forni,et al.  Antithetic integral feedback for the robust control of monostable and oscillatory biomolecular circuits , 2019, bioRxiv.

[7]  Jianhong Wu,et al.  Semiflows "Monotone with Respect to High-Rank Cones" on a Banach Space , 2017, SIAM J. Math. Anal..

[8]  Michael Margaliot,et al.  A generalization of linear positive systems with applications to nonlinear systems: Invariant sets and the Poincaré-Bendixson property , 2019, Autom..

[9]  J. Mallet-Paret,et al.  The Poincare-Bendixson theorem for monotone cyclic feedback systems , 1990 .

[10]  M. A. Krasnoselʹskii,et al.  Positive Linear Systems, the Method of Positive Operators , 1989 .

[11]  Vincent Noireaux,et al.  Some Remarks on Robust Gene Regulation in a Biomolecular Integral Controller , 2019, 2019 IEEE 58th Conference on Decision and Control (CDC).

[12]  Michael Y. Li,et al.  A Criterion for Stability of Matrices , 1998 .

[13]  Charles A. Micchelli,et al.  Total positivity and its applications , 1996 .

[14]  Allan Pinkus Totally Positive Matrices , 2009 .

[15]  R. A. Smith,et al.  The Poincaré–Bendixson theorem for certain differential equations of higher order , 1979, Proceedings of the Royal Society of Edinburgh: Section A Mathematics.

[16]  Eduardo D. Sontag,et al.  In vitro implementation of robust gene regulation in a synthetic biomolecular integral controller , 2019, Nature Communications.

[17]  A. Pinkus Spectral Properties of Totally Positive Kernels and Matrices , 1996 .

[18]  Lorenzo Marconi,et al.  Internal Models in Control, Biology and Neuroscience , 2018, 2018 IEEE Conference on Decision and Control (CDC).

[19]  Binyamin Schwarz,et al.  Totally positive differential systems , 1970 .

[20]  Wen-Chyuan Yueh EIGENVALUES OF SEVERAL TRIDIAGONAL MATRICES , 2005 .

[21]  Hal L. Smith,et al.  Monotone Dynamical Systems: An Introduction To The Theory Of Competitive And Cooperative Systems (Mathematical Surveys And Monographs) By Hal L. Smith , 1995 .

[22]  E. J. McShane,et al.  Extension of range of functions , 1934 .

[23]  Hal L. Smith Periodic tridiagonal competitive and cooperative systems of differential equations , 1991 .

[24]  M. Khammash,et al.  A universal biomolecular integral feedback controller for robust perfect adaptation , 2019, Nature.

[25]  S. Rinaldi,et al.  Positive Linear Systems: Theory and Applications , 2000 .

[26]  Michael Margaliot,et al.  Revisiting totally positive differential systems: A tutorial and new results , 2018, Autom..

[27]  Zahra Aminzarey,et al.  Contraction methods for nonlinear systems: A brief introduction and some open problems , 2014, 53rd IEEE Conference on Decision and Control.

[28]  F. Gantmacher,et al.  Oscillation matrices and kernels and small vibrations of mechanical systems , 1961 .

[29]  A. S. Elkhader A result on a feedback system of ordinary differential equations , 1992 .

[30]  Michael Margaliot,et al.  A Generalization of Linear Positive Systems , 2019, 2019 27th Mediterranean Conference on Control and Automation (MED).

[31]  James S. Muldowney,et al.  Compound matrices and ordinary differential equations , 1990 .

[32]  Shaun M. Fallat,et al.  Totally Nonnegative Matrices , 2011 .