Robust concentration and frequency control in oscillatory homeostats

PLoS One. 2014 Sep 19;9(9):e107766. doi: 10.1371/journal.pone.0107766. eCollection 2014.

Abstract

Homeostatic and adaptive control mechanisms are essential for keeping organisms structurally and functionally stable. Integral feedback is a control theoretic concept which has long been known to keep a controlled variable A robustly (i.e. perturbation-independent) at a given set-point A(set) by feeding the integrated error back into the process that generates A. The classical concept of homeostasis as robust regulation within narrow limits is often considered as unsatisfactory and even incompatible with many biological systems which show sustained oscillations, such as circadian rhythms and oscillatory calcium signaling. Nevertheless, there are many similarities between the biological processes which participate in oscillatory mechanisms and classical homeostatic (non-oscillatory) mechanisms. We have investigated whether biological oscillators can show robust homeostatic and adaptive behaviors, and this paper is an attempt to extend the homeostatic concept to include oscillatory conditions. Based on our previously published kinetic conditions on how to generate biochemical models with robust homeostasis we found two properties, which appear to be of general interest concerning oscillatory and homeostatic controlled biological systems. The first one is the ability of these oscillators ("oscillatory homeostats") to keep the average level of a controlled variable at a defined set-point by involving compensatory changes in frequency and/or amplitude. The second property is the ability to keep the period/frequency of the oscillator tuned within a certain well-defined range. In this paper we highlight mechanisms that lead to these two properties. The biological applications of these findings are discussed using three examples, the homeostatic aspects during oscillatory calcium and p53 signaling, and the involvement of circadian rhythms in homeostatic regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Biological Clocks / physiology*
  • Calcium Signaling
  • Circadian Rhythm
  • Feedback, Physiological
  • Homeostasis*
  • Kinetics
  • Models, Biological*
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Tumor Suppressor Protein p53

Grants and funding

Funding provided by Grant no. 167087/V40 by Norwegian Research Council (http://www.forskningsradet.no) for IWJ and Grant no. 183085/S10 by Norwegian Research Council (http://www.forskningsradet.no) for XYN. This research was also funded by Program Area Fund “Organelle Biology” and the Program Area Fund “Biomedical data analysis group” from the Faculty of Science and Technology, University of Stavanger (https://www.uis.no/fakulteter-institutter-og-sentre/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.