KEY PUBLICATIONS

Alternative modes of client binding enable functional plasticity of Hsp70
Alireza Mashaghi et al. | Nature 539, 448-451 (2016) | pdf & DOI: 10.1038/nature20137
Stochasticity of metabolism and growth at the single-cell level
Daniel J. Kiviet et al. | Nature 514, 376-379 (2014) | pdf & DOI: 10.1038/nature13582
Reshaping of the conformational search of a protein by the chaperone trigger factor
Alireza Mashaghi et al. | Nature 500, 98-101 (2013) | pdf & DOI: 10.1038/nature12293
Tradeoffs and optimality in the evolution of gene regulation
Frank J. Poelwijk et al. | Cell 146, 462-470 (2011) | pdf & DOI:10.1016/j.cell.2011.06.035
Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway
Philipp Bechtluft, Ruud van Leeuwen et al. | Science 318:1458-1461 (2007) | pdf & DOI:10.1126/science.1144972
Empirical fitness landscapes reveal accessible evolutionary paths
Frank Poelwijk, Daan Kiviet et al. | Nature 445:383-386 (2007) | pdf & DOI:10.1038/nature05451
The bacteriophage phi29 portal motor can package DNA against a large internal force
Douglas E. Smith, Sander J. Tans et al. | Nature 413:748-52 (2001) | pdf & DOI:10.1038/35099581
Molecular transistors: Potential modulations along carbon nanotubes
Sander J. Tans, Cees Dekker. | Nature 404:834-35 (2000) | pdf & DOI:10.1038/35009026
Imaging electron wave functions of quantized energy levels in carbon nanotubes
Liesbeth C. Venema et al. | Science 283:52-55 (1999) | pdf & DOI:10.1126/science.283.5398.52
Electron-electron correlations in carbon nanotubes
Sander J. Tans et al. | Nature 394:761-64 (1998) | pdf & DOI:10.1038/29494
Room-temperature transistor based on a single carbon nanotube
Sander J. Tans, Alwin R. M. Verschueren & Cees Dekker | Nature 393:49-52 (1998) | pdf & DOI:10.1038/29954
Individual single-wall carbon nanotubes as quantum wires
Sander J. Tans et al. | Nature 386:474-77 (1997) | pdf & DOI:10.1038/386474a0
Fullerene 'crop circles'
Jie Liu et al. | Nature 385, 780-781 (1997) | pdf & DOI:10.1038/385780b0

Stochasticity of metabolism and growth at the single-cell level

Kiviet, D. J.; Nghe, P.; Walker, N.; Boulineau, S.; Sunderlikova, V.; Tans, S. J.
Abstract:
Elucidating the role of molecular stochasticity in cellular growth is central to understanding phenotypic heterogeneity and the stability of cellular proliferation. The inherent stochasticity of metabolic reaction events should have negligible effect, because of averaging over the many reaction events contributing to growth. Indeed, metabolism and growth are often considered to be constant for fixed conditions. Stochastic fluctuations in the expression level of metabolic enzymes could produce variations in the reactions they catalyse. However, whether such molecular fluctuations can affect growth is unclear, given the various stabilizing regulatory mechanisms, the slow adjustment of key cellular components such as ribosomes, and the secretion and buffering of excess metabolites. Here we use time-lapse microscopy to measure fluctuations in the instantaneous growth rate of single cells of Escherichia coli, and quantify time-resolved cross-correlations with the expression of lac genes and enzymes in central metabolism. We show that expression fluctuations of catabolically active enzymes can propagate and cause growth fluctuations, with transmission depending on the limitation of the enzyme to growth. Conversely, growth fluctuations propagate back to perturb expression. Accordingly, enzymes were found to transmit noise to other unrelated genes via growth. Homeostasis is promoted by a noise-cancelling mechanism that exploits fluctuations in the dilution of proteins by cell-volume expansion. The results indicate that molecular noise is propagated not only by regulatory proteins but also by metabolic reactions. They also suggest that cellular metabolism is inherently stochastic, and a generic source of phenotypic heterogeneity.
Year:
2014
Type of Publication:
Article
Journal:
Nature
Volume:
514
Number:
7522
Pages:
376-379
Month:
October
Note:
[DOI:\href{https://dx.doi.org/10.1038/nature13582}{10.1038/nature13582}] [PubMed:\href{https://www.ncbi.nlm.nih.gov/pubmed/25186725}{25186725}]
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