Spatio-temporal modelling of the p53-mdm2 oscillatory system

K. E. Gordon, I. M. M. Van Leeuwen, S. Lain, M. A. J. Chaplain

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    15 Citations (Scopus)

    Abstract

    In this paper we investigate the role of spatial effects in determining the dynamics of a subclass of signalling pathways characterised by their ability to demonstrate oscillatory behaviour. To this end, we formulate a simple spatial model of the p53 network that accounts for both a negative feedback and a transcriptional delay. We show that the formation of protein density patterns can depend on the shape of the cell, position of the nucleus, and the protein diffusion rates. The temporal changes in the total amounts of protein are also subject to spatial influences. The level of DNA damage required to induce sustained oscillations, for instance, depends on the morphology of the cell. The model also provides a new interpretation of experimentally observed undamped oscillations in p53 levels in single cells. Our simulations reveal that alternate sequences of high-and low-amplitude oscillations can occur. We propose that the digital pulses may correspond to snap-shots of our high-amplitude sequences. Shorter waiting-times between subsequent time-lapse fluorescence microscopy images in combination with lower detection thresholds may reveal the irregular high-frequency oscillations suggested by our spatial model.

    Original languageEnglish
    Pages (from-to)97-116
    Number of pages20
    JournalMathematical Modelling of Natural Phenomena
    Volume4
    Issue number3
    DOIs
    Publication statusPublished - 2009

    Keywords

    • Tumour suppressor
    • Cancer
    • Signalling pathway
    • Limit cycle
    • Pulse

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