Abstract
Bimodal distributions of protein activities in signaling systems are often interpreted as indicators of underlying switch-like responses and bistable dynamics. We investigate the emergence of bimodal protein distributions by analyzing a less appreciated mechanism: oscillating signaling systems with varying amplitude, phase and frequency due to cell-to-cell variability. We support our analysis by analytical derivations for basic oscillators and numerical simulations of a signaling cascade, which displays sustained oscillations in protein activities. Importantly, we show that the time to reach the bimodal distribution depends on the magnitude of cell-to-cell variability. We quantify this time using the Kullback-Leibler divergence. The implications of our findings for single-cell experiments are discussed.
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Dobrzyński, M., Fey, D., Nguyen, L.K., Kholodenko, B.N. (2012). Bimodal Protein Distributions in Heterogeneous Oscillating Systems. In: Gilbert, D., Heiner, M. (eds) Computational Methods in Systems Biology. CMSB 2012. Lecture Notes in Computer Science(), vol 7605. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33636-2_3
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DOI: https://doi.org/10.1007/978-3-642-33636-2_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-33635-5
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