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 stepwise 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. ; publishedVersion


    Access

    Download


    Export, share and cite



    Title :

    Homeostatic controllers compensating for growth and perturbations


    Contributors:

    Publication date :

    2019-08-22


    Remarks:

    cristin:1717881
    39 ; 14 ; PLOS ONE ; 8



    Type of media :

    Article (Journal)


    Type of material :

    Electronic Resource


    Language :

    English



    Classification :

    DDC:    629




    Homeostatic flying hovercraft

    PEDERSEN BRAD / SPIROV PETER | European Patent Office | 2015

    Free access

    Homeostatic image perception: An artificial system

    Feldman, T. / Younes, L. | British Library Online Contents | 2006


    Homeostatic tendencies of the Earth's atmosphere

    Lovelock, James E. / Margulis, Lynn | Online Contents | 1974


    Compensating radiometer

    Anderson, W. W., Jr. / Miller, H. B. / Sweet, G. E. | NTRS | 1969


    STEERING TORQUE COMPENSATING APPARATUS AND STEERING TORQUE COMPENSATING METHOD

    KIM SOON TAE | European Patent Office | 2016

    Free access