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Emergent properties of coupled bistable switches

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Abstract

Understanding the dynamical hallmarks of network motifs is one of the fundamental aspects of systems biology. Positive feedback loops constituting one or two nodes – self-activation, toggle switch, and double activation loops – are the commonly observed motifs in regulatory networks underlying cell-fate decision systems. Their individual dynamics are well studied; they are capable of exhibiting bistability. However, studies across various biological systems suggest that such positive feedback loops are interconnected with one another, and design principles of coupled bistable motifs remain unclear. What happens to the bistability or multistability traits and the phenotypic space (collection of phenotypes exhibited by a system) due to the couplings? In this study, we explore a set of such interactions using discrete and continuous simulation methods. Our results suggest that the most frequent states in coupled networks follow the ‘rules’ within a motif (double activation, toggle switch) and those across the two motifs in terms of how the two motifs have been coupled. Moreover, ‘hybrid’ states can be observed, too, where one of the above-mentioned ‘rules’ can be compromised, leading to a more diverse phenotypic repertoire. Furthermore, adding direct and indirect self-activations to these coupled networks can increase the frequency of multistability. Thus, our observations revealed specific dynamical traits exhibited by various coupled bistable motifs.

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Funding

MKJ was supported by the Infosys Foundation, Bangalore, and by the Ramanujan Fellowship awarded by Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Government of India (SB/S2/RJN-049/2018). KH and ASD were supported by the Prime Minister’s Research Fellowship, Government of India.

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Author notes

  1. Kishore Hari and Pradyumna Harlapur contributed equally to this work.

Authors and Affiliations

  1. Centre for BioSystems Science and Engineering, Indian Institute of Science, Bengaluru, India

    Kishore Hari, Atchuta Srinivas Duddu & Mohit Kumar Jolly

  2. Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India

    Pradyumna Harlapur

  3. Department of Biotechnology, R V College of Engineering, Bengaluru, India

    Aditi Gopalan & Varun Ullanat

Authors
  1. Kishore Hari
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  2. Pradyumna Harlapur
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  3. Aditi Gopalan
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  4. Varun Ullanat
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  5. Atchuta Srinivas Duddu
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  6. Mohit Kumar Jolly
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Contributions

MKJ and KH designed research; KH, PH, AG, and VU carried out simulations; KH, PH, and ASD analyzed data; all authors discussed results and prepared the paper; MKJ supervised the research. KH and PH contributed equally and are thus listed as co-first authors; they can switch the sequence of their names in their CVs.

Corresponding author

Correspondence to Mohit Kumar Jolly.

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The authors declare no conflict of interest.

Additional information

Corresponding editor: Ravindra Venkatramani

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Hari, K., Harlapur, P., Gopalan, A. et al. Emergent properties of coupled bistable switches. J Biosci 47, 81 (2022). https://doi.org/10.1007/s12038-022-00310-6

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  • DOI: https://doi.org/10.1007/s12038-022-00310-6

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