CUED Publications database

Fundamental limits on the suppression of molecular fluctuations.

Lestas, I and Vinnicombe, G and Paulsson, J (2010) Fundamental limits on the suppression of molecular fluctuations. Nature, 467. pp. 174-178.

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Negative feedback is common in biological processes and can increase a system's stability to internal and external perturbations. But at the molecular level, control loops always involve signalling steps with finite rates for random births and deaths of individual molecules. Here we show, by developing mathematical tools that merge control and information theory with physical chemistry, that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctuations. Specifically, the minimum standard deviation in abundances decreases with the quartic root of the number of signalling events, making it extremely expensive to increase accuracy. Our results are formulated in terms of experimental observables, and existing data show that cells use brute force when noise suppression is essential; for example, regulatory genes are transcribed tens of thousands of times per cell cycle. The theory challenges conventional beliefs about biochemical accuracy and presents an approach to the rigorous analysis of poorly characterized biological systems.

Item Type: Article
Uncontrolled Keywords: Animals Cell Physiological Phenomena Entropy Feedback Gene Expression Regulation Models, Biological Signal Transduction Systems Biology
Divisions: Div F > Control
Div B > Electronics, Power & Energy Conversion
Depositing User: Unnamed user with email
Date Deposited: 17 Jul 2017 19:07
Last Modified: 09 Sep 2021 02:24
DOI: 10.1038/nature09333