Antagonistic regulation with a unique setpoint, integral and double integral action

Thorsen, Kristian; Ruoff, Peter; Drengstig, Tormod

doi:10.1101/248682

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…In our previous work [18] only outflow perturbations were considered, because the central feedback loop A - e - E - A in Fig 4 (being an inflow controller) compensates essentially for outflow perturbations in A [31]. However, since the I 1 - I 2 ‘outer feedback layer’ in Fig 4 should also allow to compensate for inflows to A as implied by the work of Thorsen [52], I tested the coherent feedback scheme with respect to inflow perturbations to A . In Fig 5 we have the same rate constants and perturbative conditions as in Fig 3, but keep both A and E under homeostatic control by I 1 and I 2 (see Figs 5a and b).…”

Section: Resultsmentioning

confidence: 99%

Background compensation revisited: Conserved phase response curves in frequency controlled homeostats with coherent feedback

Ruoff

2024

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Background compensation is the ability of a controlled variable to respond to an applied perturbation in an unchanged manner and independent of different but constant background signals which act in parallel to the perturbation. We found that background compensation occurs by ‘coherent feedback’ mechanisms where additional control variables feed directly back to the controlled variable. This paper extends a previous study on background compensation to include phase responses in frequency controlled coherent feedback oscillators. While the frequency resetting amplitude in coherent feedback oscillators is found to be dependent on the inflow/outflow perturbation of the controlled variable and thereby become phase dependent, the frequency resetting itself and the corresponding phase response curves are found to be background compensated. It is speculated that this type of background compensation may be an additional way how ambient noise can be ‘ignored’ by organisms.

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Section: Resultsmentioning

confidence: 99%

Background compensation revisited: Conserved phase response curves in frequency controlled homeostats with coherent feedback

Ruoff

2024

Preprint

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“…Similar to controllers based on double integral action [24] an autocatalytic design [19] is able to keep the controlled species at its set-point even when perturbations become linearly time dependent and rapid [18]. However, in contrast to double integral action the autocatalytic controller is able to compensate for time-dependent perturbations of the form a ⋅ t n where n is larger than 1.…”

Section: Case A1: Controllers With Transporter-based Compensatory Flmentioning

confidence: 99%

Homeostatic controllers compensating for growth and perturbations

et al. 2019

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Cells and organisms have developed homeostatic mechanisms which protect them against a changing environment. How growth and homeostasis interact is still not well understood, but of increasing interest to the molecular and synthetic biology community to recognize and design control circuits which can oppose the diluting effects of cell growth. In this paper we describe the performance of selected negative feedback controllers in response to different applied growth laws and time dependent outflow perturbations of a controlled variable. The approach taken here is based on deterministic mass action kinetics assuming that cell content is instantaneously mixed. All controllers behave ideal in the sense that they for step-wise perturbations in volume and a controlled compound A are able to drive A precisely back to the controllers’ theoretical set-points. The applied growth kinetics reflect experimentally observed growth laws, which range from surface to volume ratio growth to linear and exponential growth. Our results show that the kinetic implementation of integral control and the structure of the negative feedback loop are two properties which affect controller performance. Best performance is observed for controllers based on derepression kinetics and controllers with an autocatalytic implementation of integral control. Both are able to defend exponential growth and perturbations, although the autocatalytic controller shows an offset from its theoretical set-point. Controllers with activating signaling using zero-order or bimolecular (antithetic) kinetics for integral control behave very similar but less well. Their performance can be improved by implementing negative feedback structures having repression/derepression steps or by increasing controller aggressiveness. Our results provide a guide what type of feedback structures and integral control kinetics are suitable to oppose the dilution effects by different growth laws and time dependent perturbations on a deterministic level.

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Homeostatic Controllers Compensating for Growth and Perturbations

Ruoff

Agafonov

Tveit

et al. 2018

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authors contributed equally to this work.Abstract 1 Cells and organisms have developed homeostatic mechanisms to maintain internal 2 stabilities which protect them against a changing environment. How cellular growth and 3 homeostasis interact is still not well understood, but of increasing interest to the 4 synthetic and molecular biology community where molecular control circuits are sought 5 and tried to maintain homeostasis that opposes the diluting effects of cell growth. In 6 this paper we describe the performance of four negative feedback (inflow) controllers, 7 which, for different observed growth laws (time-dependent increase in the cellular 8 volume V ) are able to compensate for various time-dependent removals of the controlled 9 variable A. The four implementations of integral control are based on zero-order, 10 first-order autocatalytic, second-order (antithetic), and derepressing inhibition kinetics. 11 All controllers behave ideal in the sense that they for step-wise perturbations in V and 12 A are able to drive the controlled variable precisely back to the controller's theoretical 13 set-point A theor set . The applied increase in cellular volume includes linear, exponential 14 and saturating growth and reflect experimentally observed growth laws of single cell 15 organisms and other cell types. During the increase in V , additional linear or 16 exponentialtime-dependent perturbations which remove A are applied, and controllers 17 are tested with respect to their ability to compensate for both the increase in volume V 18 and the applied perturbations removing A. Our results show that the way how integral 19 control is kinetically implemented and the structure of the negative feedback loop are 20 essential determinants of a controller's performance. The results provide a ranking 21 between the four tested controller types. Considering exponential volume increases 22 together with an exponentially increasing removal rate of A controllers based on 23 derepression kinetics perform best, but break down when the control-inhibitor's 24 concentration gets too low. The first-order autocatalytic controller is able to defend 25 time-dependent exponential growth and removals in A, but generally with a certain 26 PLOS 1/23 offset below its theoretical set-point A theor set . The controllers based on zero-order and 27 second-order (antithetic) integral feedback can only manage linear increases in V and 28 removals in A, in dependence of the controllers' aggressiveness. Our results provide a 29 theoretical basis what controller kinetics are needed in order to compensate for different 30 growth laws. 31 70 because together with the diluting effects of the different growth laws these 71 perturbations represent the most severe conditions for testing the controllers. 72 PLOS 2/23 115 PLOS 3/23 130 Cell internal generated A 131 Compensatory fluxes to counteract diminishing levels of a controlled compound A can 132 be generated by a cell internal compound (assumed here to be homogeneously 133 distributed inside V ) or ...

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Antagonistic regulation with a unique setpoint, integral and double integral action

Cited by 3 publications

References 27 publications

Background compensation revisited: Conserved phase response curves in frequency controlled homeostats with coherent feedback

Background compensation revisited: Conserved phase response curves in frequency controlled homeostats with coherent feedback

Homeostatic controllers compensating for growth and perturbations

Homeostatic Controllers Compensating for Growth and Perturbations

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