Performance of Homeostatic Controller Motifs Dealing with Perturbations of Rapid Growth and Depletion.

An essential property of life is that cells and organisms have the ability to protect themselves against external disturbances/attacks by using homeostatic mechanisms. These defending mechanisms are based on negative feedback regulation and often contain additional features, such as integral control, where the integrated error between a controlled variable and its set-point is used to achieve homeostasis. Although the concept of integral control has its origin in industrial processes, recent findings suggest that biological systems are also capable of showing integral control. We recently described a basic set of negative feedback structures (controller motifs) where robust homeostasis is achieved against different but constant perturbations. As many perturbations in biology, such as infections, increase rapidly over time, we investigated how the different controller motifs equipped with different implementations of integral control perform in relation to rapidly changing perturbations, including exponential and hyperbolic changes. The findings show that the construction of an optimum biochemical controller design for time-dependent perturbations requires a certain match between the structure of the negative feedback loop, its signaling kinetics, and the kinetics of how integral control is implemented within the negative feedback loop.

[1]  W. Cannon.  ORGANIZATION FOR PHYSIOLOGICAL HOMEOSTASIS , 1929 .

[2]  W. Cannon.  The Wisdom of the Body , 1932 .

[3]  H. Selye.  EXPERIMENTAL EVIDENCE SUPPORTING THE CONCEPTION OF "ADAPTATION ENERGY" , 1938 .

[4]  H. Selye,et al.  Adaptation Energy , 1938, Nature.

[5]  Norbert Wiener,et al.  Cybernetics, or control and communication in the animal and the machine, 2nd ed. , 1961 .

[6]  B. Goodwin.  Temporal organization in cells , 1963 .

[7]  D. Baron.  Advances in Enzyme Regulation, Vol 4. , 1967 .

[8]  C. Ladd Prosser,et al.  Homeostasis. Origins of the concept , 1976, Medical History.

[9]  Bruce A. Francis,et al.  The internal model principle of control theory , 1976, Autom..

[10]  M. Moore-Ede,et al.  Physiology of the circadian timing system: predictive versus reactive homeostasis. , 1986, The American journal of physiology.

[11]  J. T. Reason,et al.  Handbook of Life Stress, Cognition and Health , 1988 .

[12]  A. Isidori,et al.  Output regulation of nonlinear systems , 1990 .

[13]  M. Eigen,et al.  The hypercycle. Coupling of RNA and protein biosynthesis in the infection cycle of an RNA bacteriophage. , 1991, Biochemistry.

[14]  Alan C. Hindmarsh,et al.  Description and use of LSODE, the Livermore Solver for Ordinary Differential Equations , 1993 .

[15]  B. Goodwin.  Temporal organization and disorganization in organisms. , 1997, Chronobiology international.

[16]  J H Koeslag,et al.  Integral rein control in physiology. , 1998, Journal of theoretical biology.

[17]  J. Doyle,et al.  Robust perfect adaptation in bacterial chemotaxis through integral feedback control. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Sonia Cortassa,et al.  Why Homeodynamics, Not Homeostasis? , 2001, TheScientificWorldJournal.

[19]  Jay Schulkin.  Rethinking Homeostasis: Allostatic Regulation in Physiology and Pathophysiology , 2002 .

[20]  M. Khammash,et al.  Calcium homeostasis and parturient hypocalcemia: an integral feedback perspective. , 2002, Journal of theoretical biology.

[21]  A. Khaled,et al.  Lymphocide: cytokines and the control of lymphoid homeostasis , 2002, Nature Reviews Immunology.

[22]  Eduardo D. Sontag,et al.  Adaptation and regulation with signal detection implies internal model , 2003, Syst. Control. Lett..

[23]  G. Cook,et al.  Hyperbolic growth of Thermoanaerobacter thermohydrosulfuricus (Clostridium thermohydrosulfuricum) increases ethanol production in pH-controlled batch culture , 1994, Applied Microbiology and Biotechnology.

[24]  Jay Schulkin,et al.  Allostasis, Homeostasis, and the Costs of Physiological Adaptation: Preface , 2004 .

[25]  P. Ruoff,et al.  The control of the controller: molecular mechanisms for robust perfect adaptation and temperature compensation. , 2009, Biophysical journal.

[26]  D. Firsov,et al.  Circadian clock and the concept of homeostasis , 2009, Cell cycle.

[27]  Peter Ruoff,et al.  Harmonic oscillations in homeostatic controllers: Dynamics of the p53 regulatory system. , 2010, Biophysical journal.

[28]  Brian Ingalls,et al.  Considerations for using integral feedback control to construct a perfectly adapting synthetic gene network. , 2010, Journal of theoretical biology.

[29]  T Drengstig,et al.  A basic set of homeostatic controller motifs. , 2012, Biophysical journal.

[30]  T Drengstig,et al.  Robust adaptation and homeostasis by autocatalysis. , 2012, The journal of physical chemistry. B.

[31]  Didier Gonze,et al.  The Goodwin Model: Behind the Hill Function , 2013, PloS one.

[32]  Jordan Ang,et al.  Physical constraints on biological integral control design for homeostasis and sensory adaptation. , 2013, Biophysical journal.

[33]  P. Ruoff,et al.  Robust Concentration and Frequency Control in Oscillatory Homeostats , 2014, PloS one.

[34]  P. Ruoff,et al.  Transepithelial glucose transport and Na+/K+ homeostasis in enterocytes: an integrative model. , 2014, American journal of physiology. Cell physiology.

[35]  P. Ruoff,et al.  The Organization of Controller Motifs Leading to Robust Plant Iron Homeostasis , 2016, PloS one.

[36]  P. Ruoff,et al.  Modeling the diversion of primary carbon flux into secondary metabolism under variable nitrate and light/dark conditions. , 2016, Journal of theoretical biology.

[37]  T. A. Tyukina,et al.  Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death. , 2015, Journal of theoretical biology.