Evidence map›Paper›PMID 26501750›Full record

ArticleNature nanotechnology2016

Macromolecular crowding creates heterogeneous environments of gene expression in picolitre droplets.

Maike M K Hansen, Lenny H H Meijer, Evan Spruijt, Roel J M Maas, Marta Ventosa Rosquelles, Joost Groen, Hans A Heus, Wilhelm T S Huck

Abstract read
In one paragraph

Article in Nature nanotechnology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed.

  1. Article
  2. Reconstituting alternative life using the test-bed of cell-free systems.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
  3. Article
  4. Macromolecule-Driven Supramolecular Polymerization Induced by Crowding Effects.Angewandte Chemie (International ed. in English) · 2025
    Article
  5. Article
  6. Review
  7. Crowding in Anhydrobiosis.Sub-cellular biochemistry · 2025
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Bottom-Up Synthetic Biology Using Cell-Free Protein Synthesis.Advances in biochemical engineering/biotechnology · 2023
    Review
  18. Compartmentalized Cell-Free Expression Systems for Building Synthetic Cells.Advances in biochemical engineering/biotechnology · 2023
    Article
  19. High Macromolecular Crowding in Liposomes from Microfluidics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Maike M K HansenRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Lenny H H MeijerEindhoven University of Technology, Institute for Complex Molecular Systems and Computational Biology Group, Eindhoven 5600 MB, The Netherlands.
Evan SpruijtESPCI ParisTech, Laboratoire de Physique et Mécanique des Milieux Hétérogènes, UMR 7636 du CNRS, Paris 75005, France.
Roel J M MaasRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Marta Ventosa RosquellesRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Joost GroenRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Hans A HeusRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Wilhelm T S HuckRadboud University, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

Funding

European Research Council 246812
6 · The paper itself

Abstract

Understanding the dynamics of complex enzymatic reactions in highly crowded small volumes is crucial for the development of synthetic minimal cells. Compartmentalized biochemical reactions in cell-sized containers exhibit a degree of randomness due to the small number of molecules involved. However, it is unknown how the physical environment contributes to the stochastic nature of multistep enzymatic processes. Here, we present a robust method to quantify gene expression noise in vitro using droplet microfluidics. We study the changes in stochasticity in the cell-free gene expression of two genes compartmentalized within droplets as a function of DNA copy number and macromolecular crowding. We find that decreased diffusion caused by a crowded environment leads to the spontaneous formation of heterogeneous microenvironments of mRNA as local production rates exceed the diffusion rates of macromolecules. This heterogeneity leads to a higher probability of the molecular machinery staying in the same microenvironment, directly increasing the system's stochasticity.

Indexed as

Escherichia coliGene ExpressionMacromolecular SubstancesNanotechnologyRNA, MessengerSynthetic BiologyMacromolecular SubstancesRNA, Messenger

Identifiers

PMID26501750
PMCPMC4740931

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.