The Bacterial Cytoplasm Has Glass-like Properties and Is Fluidized by Metabolic Activity
Open accessAbstract
The physical nature of the bacterial cytoplasm is poorly understood even though it determines cytoplasmic dynamics and hence cellular physiology and behavior. Through single-particle tracking of protein filaments, plasmids, storage granules, and foreign particles of different sizes, we find that the bacterial cytoplasm displays properties that are characteristic of glass-forming liquids and changes from liquid-like to solid-like in a component size-dependent fashion. As a result, the motion of cytoplasmic components becomes disproportionally constrained with increasing size. Remarkably, cellular metabolism fluidizes the cytoplasm, allowing larger components to escape their local environment and explore larger regions of the cytoplasm. Consequently, cytoplasmic fluidity and dynamics dramatically change as cells shift between metabolically active and dormant states in response to fluctuating environments. Our findings provide insight into bacterial dormancy and have broad implications to our understanding of bacterial physiology, as the glassy behavior of the cytoplasm impacts all intracellular processes involving large components.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The complex molecular mixture is animated by both thermally driven diffusion and metabolism, which plays a key role in maintaining the cell interior in a fluid state.
“This complex molecular mixture is animated by both thermally driven diffusion and metabolism, which plays a key role in maintaining the cell interior in a fluid state.38”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Zimmerman, S. B., & Trach, S. O. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90499-v · Cited by 1,337 · see citing works
Flagged first, then by citations
Research works printed but not linked: 45
- Ausmees N Kuhn JR Jacobs-Wagner C 2003 The bacterial cytoskeleton: an intermediate filament-like function in cell shape Cell 115 705 713 14675535
- Bakshi S Bratton BP Weisshaar JC 2011 Subdiffraction-limit study of Kaede diffusion and spatial distribution in live Escherichia coli Biophys J 101 2535 2544 22098753 PMC3218334
- Brangwynne CP Koenderink GH MacKintosh FC Weitz DA 2009 Intracellular transport by active diffusion Trends Cell Biol 19 423 427 19699642
- Broering TJ Arnold MM Miller CL Hurt JA Joyce PL Nibert ML 2005 Carboxyl-proximal regions of reovirus nonstructural protein muNS necessary and sufficient for forming factory-like inclusions J Virol 79 6194 6206 15858004 PMC1091696
- Broering TJ Parker JS Joyce PL Kim J Nibert ML 2002 Mammalian reovirus nonstructural protein microNS forms large inclusions and colocalizes with reovirus microtubule-associated protein micro2 in transfected cells J Virol 76 8285 8297 12134034 PMC155143
- Cabeen MT Charbon G Vollmer W Born P Ausmees N Weibel DB Jacobs-Wagner C 2009 Bacterial cell curvature through mechanical control of cell growth EMBO J 28 1208 1219 19279668 PMC2683044
- Cabeen MT Murolo MA Briegel A Bui NK Vollmer W Ausmees N Jensen GJ Jacobs-Wagner C 2010 Mutations in the Lipopolysaccharide biosynthesis pathway interfere with crescentin-mediated cell curvature in Caulobacter crescentus J Bacteriol 192 3368 3378 20435724 PMC2897673
- Cayley S Lewis BA Guttman HJ Record MT Jr 1991 Characterization of the cytoplasm of Escherichia coli K-12 as a function of external osmolarity. Implications for protein-DNA interactions in vivo J Mol Biol 222 281 300 1960728
- Coates ARM 2003 Dormancy and low-growth states in microbial disease Cambridge; New York Cambridge University Press
- Coquel AS Jacob JP Primet M Demarez A Dimiccoli M Julou T Moisan L Lindner AB Berry H 2013 Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect PLoS Comp Biol 9 e1003038 PMC3636022 23633942
- Derman AI Lim-Fong G Pogliano J 2008 Intracellular mobility of plasmid DNA is limited by the ParA family of partitioning systems Mol Microbiol 67 935 946 18208495
- Dix JA Verkman AS 2008 Crowding effects on diffusion in solutions and cells Ann Rev Biophys 37 247 263 18573081
- Elowitz MB Surette MG Wolf PE Stock JB Leibler S 1999 Protein mobility in the cytoplasm of Escherichia coli J Bacteriol 181 197 203 9864330 PMC103549
- Ely B 1991 Genetics of Caulobacter crescentus Meth Enzymol 204 372 384 1658564
- English BP Hauryliuk V Sanamrad A Tankov S Dekker NH Elf J 2011 Single-molecule investigations of the stringent response machinery in living bacterial cells Proc Nat Acad Sci USA 108 E365 E373 21730169 PMC3150888
- Fabry B Maksym GN Butler JP Glogauer M Navajas D Fredberg JJ 2001 Scaling the microrheology of living cells Phys Rev Lett 87 148102 11580676
- Fehr T Lowen H 1995 Glass-transition in confined geometry Phys Rev E 52 4016 4025 9963874
- Golding I Cox EC 2006 Physical nature of bacterial cytoplasm Phys Rev Lett 96 098102 16606319
- Heun P Laroche T Shimada K Furrer P Gasser SM 2001 Chromosome dynamics in the yeast interphase nucleus Science 294 2181 2186 11739961
- Hunter GL Weeks ER 2012 The physics of the colloidal glass transition Rep Prog Phys 75 066501 22790649
- Hwang LC Vecchiarelli AG Han YW Mizuuchi M Harada Y Funnell BE Mizuuchi K 2013 ParA-mediated plasmid partition driven by protein pattern self-organization EMBO J 32 1238 49 23443047 PMC3642677
- Jun S Wright A 2010 Entropy as the driver of chromosome segregation Nat Rev Microbiol 8 600 607 20634810 PMC3148256
- Kegel WK van Blaaderen A 2000 Direct observation of dynamical heterogeneities in colloidal hard-sphere suspensions Science 287 290 293 10634780
- Latulippe DR Zydney AL 2010 Radius of gyration of plasmid DNA isoforms from static light scattering Biotechnol Bioeng 107 134 142 20506212
- Lennon JT Jones SE 2011 Microbial seed banks: the ecological and evolutionary implications of dormancy Nat Rev Microbiol 9 119 130 21233850
- Levi V Ruan Q Plutz M Belmont AS Gratton E 2005 Chromatin dynamics in interphase cells revealed by tracking in a two-photon excitation microscope Biophys J 89 4275 4285 16150965 PMC1366992
- Maehara A Taguchi S Nishiyama T Yamane T Doi Y 2002 A repressor protein, PhaR, regulates polyhydroxyalkanoate (PHA) synthesis via its direct tnteraction with PHA J Bacteriol 184 3992 4002 12081972 PMC135160
- Marcus AH Schofield J Rice SA 1999 Experimental observations of non-Gaussian behavior and stringlike cooperative dynamics in concentrated quasi-two-dimensional colloidal liquids Phys Rev E 60 5725 5736 11970468
- Mika JT van den Bogaart G Veenhoff L Krasnikov V Poolman B 2010 Molecular sieving properties of the cytoplasm of Escherichia coli and consequences of osmotic stress Mol Microbiol 77 200 207 20487282
- Montero Llopis P Sliusarenko O Heinritz J Jacobs-Wagner C 2012 In vivo biochemistry in bacterial cells using FRAP: insight into the translation cycle Biophys J 103 1848 1859 23199913 PMC3491719
- Nenninger A Mastroianni G Mullineaux CW 2010 Size dependence of protein diffusion in the cytoplasm of Escherichia coli J Bacteriol 192 4535 4540 20581203 PMC2937421
- Niu L Yu J 2008 Investigating intracellular dynamics of FtsZ cytoskeleton with photoactivation singlemolecule tracking Biophys J 95 2009 2016 18390602 PMC2483766
- Petekidis G Moussaid A Pusey PN 2002 Rearrangements in hard-sphere glasses under oscillatory shear strain Phys Rev E 66 051402 12513487
- Qi QS Rehm BHA 2001 Polyhydroxybutyrate biosynthesis in Caulobacter crescentus: molecular characterization of the polyhydroxybutyrate synthase Microbiol 147 3353 3358 11739767
- Sliusarenko O Heinritz J Emonet T Jacobs-Wagner C 2011 High-throughput, subpixel precision analysis of bacterial morphogenesis and intracellular spatio-temporal dynamics Mol Microbiol 80 612 627 21414037 PMC3090749
- Soutoglou E Misteli T 2007 Mobility and immobility of chromatin in transcription and genome stability Curr Opin Gen Dev 17 435 442 PMC2118061 17905579
- Spitzer J 2011 From water and ions to crowded biomacromolecules: in vivo structuring of a prokaryotic cell Microbiol Mol Biol Rev 75 491 506 21885682 PMC3165543
- Spitzer J Poolman B 2009 The role of biomacromolecular crowding, ionic strength, and physicochemical gradients in the complexities of life’s emergence Microbiol Mol Biol Rev 73 371 388 19487732 PMC2698416
- Swaminathan R Hoang CP Verkman AS 1997 Photobleaching recovery and anisotropy decay of green fluorescent protein GFP-S65T in solution and cells: cytoplasmic viscosity probed by green fluorescent protein translational and rotational diffusion Biophys J 72 1900 1907 9083693 PMC1184383
- Vecchiarelli AG Hwang LC Mizuuchi K 2013 Cell-free study of F plasmid partition provides evidence for cargo transport by a diffusion-ratchet mechanism Proc Nat Acad Sci USA 110 E1390 7 23479605 PMC3625265
- Weber SC Spakowitz AJ Theriot JA 2010 Bacterial chromosomal loci move subdiffusively through a viscoelastic cytoplasm Phys Rev Lett 104 238102 20867274 PMC4929007
- Weber SC Spakowitz AJ Theriot JA 2012 Nonthermal ATP-dependent fluctuations contribute to the in vivo motion of chromosomal loci Proc Nat Acad Sci USA 109 7338 7343 22517744 PMC3358901
- Weeks E Weitz D 2002 Properties of cage rearrangements observed near the colloidal glass transition Phys Rev Lett 89 095704 12190415
- Weeks ER Crocker JC Levitt AC Schofield A Weitz DA 2000 Three-dimensional direct imaging of structural relaxation near the colloidal glass transition Science 287 627 631 10649991
- Zaccarelli E Mayer C Asteriadi A Likos C Sciortino F Roovers J Iatrou H Hadjichristidis N Tartaglia P Löwen H 2005 Tailoring the flow of soft glasses by soft additives Phys Rev Lett 95 268301 16486412
Cited by
Sorted by citations
Harmon, T. S., Holehouse, A. S., Rosen, M. K., & Pappu, R. V. (2017) · eLife · doi:10.7554/elife.30294 · Cited by 713 · see citing works
Phagocytosis: Receptors, signal integration, and the cytoskeleton
Freeman, S. A., & Grinstein, S. (2014) · Immunological Reviews · doi:10.1111/imr.12212 · Cited by 548 · see citing works
Making the Case for Disordered Proteins and Biomolecular Condensates in Bacteria
Cohan, M. C., & Pappu, R. V. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.04.011 · Cited by 104 · see citing works
Kimmel, J. C., Chang, A. Y., Brack, A. S., & Marshall, W. F. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1005927 · Cited by 54 · see citing works
“The Heteromotility software also considers the non-Gaussian parameter α2, for which larger values indicate a more heavily tailed, Levy flight-like distribution [53, 54].”
MethodMetals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
Dynamics of chromosome organization in a minimal bacterial cell
Gilbert, B. R., Thornburg, Z. R., Brier, T. A., Stevens, J. A., Grünewald, F., Stone, J. E., Marrink, S. J., & Luthey-Schulten, Z. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1214962 · Cited by 19 · see citing works
Viscosity and diffusion in life processes and tuning of fundamental constants
Trachenko, K. (2023) · Reports on Progress in Physics · doi:10.1088/1361-6633/acfd3e · Cited by 14 · see citing works
- Authors
- Parry, B. R., Surovtsev, I. V., Cabeen, M. T., O’Hern, C. S., Dufresne, E. R., & Jacobs-Wagner, C.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 1-2
- Pages
- 183-194
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3956598
- OpenAlex
- W2161435888
- Cited by
- 822
- References
- 1
- Citations by year
- 2026: 62 · 2025: 73 · 2024: 88 · 2023: 96 · 2022: 65 · 2021: 63 · 2020: 77 · 2019: 57 · 2018: 62 · 2017: 61 · 2016: 42 · 2015: 42 · 2014: 34
- FWCI
- 16.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5t32hg003198-10)
- National Human Genome Research Institute (T32-HG 003198)
- National Institute of General Medical Sciences (GM065835, R01GM065835)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Material Dynamics and Properties
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- bacterial cytoplasm, glassy state, metabolic activity, bacterial dormancy, single-particle tracking, cytoplasmic viscosity, plasmids, storage granules, protein filaments, size-dependent diffusion, intracellular transport
- MeSH terms
- Chromosomes, Bacterial, Cytoplasm, Escherichia coli, Plasmids, Caulobacter crescentus, Biophysical Phenomena
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
