Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Self-organization and positioning of bacterial protein clusters

Nature Physics volume 13, pages 1006–1013 (2017)Cite this article

Subjects

Abstract

Many cellular processes require proteins to be precisely positioned within the cell. In some cases this can be attributed to passive mechanisms such as recruitment by other proteins in the cell or by exploiting the curvature of the membrane. However, in bacteria, active self-positioning is likely to play a role in multiple processes, including the positioning of the future site of cell division and cytoplasmic protein clusters. How can such dynamic clusters be formed and positioned? Here, we present a model for the self-organization and positioning of dynamic protein clusters into regularly repeating patterns based on a phase-locked Turing pattern. A single peak in the concentration is always positioned at the midpoint of the model cell, and two peaks are positioned at the midpoint of each half. Furthermore, domain growth results in peak splitting and pattern doubling. We argue that the model may explain the regular positioning of the highly conserved structural maintenance of chromosomes complexes on the bacterial nucleoid and that it provides an attractive mechanism for the self-positioning of dynamic protein clusters in other systems.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A self-positioning Turing pattern.
Figure 2: Pattern splitting during exponential domain growth.
Figure 3: The model provides an explanation for MukBEF clustering and splitting.
Figure 4: Effects of inhomogeneous binding during exponential growth.

Similar content being viewed by others

References

  1. Murray, J. D. Mathematical Biology II: Spatial Models and Biomedical Applications (Springer, 2003).

    MATH  Google Scholar 

  2. Turing, A. M. The chemical basis of morphogenesis. Phil. Trans. R. Soc. Lond. B 237, 37–72 (1952).

    ADS  MathSciNet  MATH  Google Scholar 

  3. Kondo, S. & Miura, T. Reaction-diffusion model as a framework for understanding biological pattern formation. Science 329, 1616–1620 (2010).

    ADS  MathSciNet  MATH  Google Scholar 

  4. Raspopovic, J., Marcon, L., Russo, L. & Sharpe, J. Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients. Science 345, 566–570 (2014).

    ADS  Google Scholar 

  5. Levine, H. & Rappel, W.-J. Membrane-bound Turing patterns. Phys. Rev. E 72, 61912 (2005).

    ADS  MathSciNet  Google Scholar 

  6. Rauch, E. M. & Millonas, M. M. The role of trans-membrane signal transduction in turing-type cellular pattern formation. J. Theor. Biol. 226, 401–407 (2004).

    MathSciNet  Google Scholar 

  7. Wingreen, N. S. & Huang, K. C. Physics of intracellular organization in bacteria. Annu. Rev. Microbiol. 69, 361–379 (2015).

    Google Scholar 

  8. Monahan, L. G., Liew, A. T. F., Bottomley, A. L. & Harry, E. J. Division site positioning in bacteria: one size does not fit all. Front. Microbiol. 5, 1–7 (2014).

    Google Scholar 

  9. Rudner, D. Z. & Losick, R. Protein subcellular localization in bacteria. Cold Spring Harb. Perspect. Biol. 2, a000307 (2010).

    Google Scholar 

  10. Thalmeier, D., Halatek, J. & Frey, E. Geometry-induced protein pattern formation. Proc. Natl Acad. Sci. USA 113, 548–553 (2016).

    ADS  Google Scholar 

  11. Goryachev, A. B. & Pokhilko, A. V. Dynamics of Cdc42 network embodies a Turing-type mechanism of yeast cell polarity. FEBS Lett. 582, 1437–1443 (2008).

    Google Scholar 

  12. Arcuri, P. & Murray, J. D. Pattern sensitivity to boundary and initial conditions in reaction-diffusion models. J. Math. Biol. 24, 141–165 (1986).

    MathSciNet  MATH  Google Scholar 

  13. Woolley, T. E., Baker, R. E., Gaffney, E. A. & Maini, P. K. Stochastic reaction and diffusion on growing domains: understanding the breakdown of robust pattern formation. Phys. Rev. E 84, 46216 (2011).

    ADS  Google Scholar 

  14. Bard, J. & Lauder, I. How well does Turing’s theory of morphogenesis work? J. Theor. Biol. 45, 501–531 (1974).

    Google Scholar 

  15. Murray, J. D. Parameter space for turing instability in reaction diffusion mechanisms: a comparison of models. J. Theor. Biol. 98, 143–163 (1982).

    MathSciNet  Google Scholar 

  16. Maini, P. K., Woolley, T. E., Baker, R. E., Gaffney, E. A. & Seirin Lee, S. Turing’s model for biological pattern formation and the robustness problem. Interface Focus 2, 487–496 (2012).

    Google Scholar 

  17. Loose, M., Kruse, K. & Schwille, P. Protein self-organization: lessons from the min system. Annu. Rev. Biophys. 40, 315–336 (2011).

    Google Scholar 

  18. Nolivos, S. & Sherratt, D. J. The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes. FEMS Microbiol. Rev. 38, 380–392 (2014).

    Google Scholar 

  19. Rybenkov, V. V., Herrera, V., Petrushenko, Z. M. & Zhao, H. MukBEF, a chromosomal organizer. J. Mol. Microbiol. Biotechnol. 24, 371–383 (2014).

    Google Scholar 

  20. Cui, Y., Petrushenko, Z. M. & Rybenkov, V. V. MukB acts as a macromolecular clamp in DNA condensation. Nat. Struct. Mol. Biol. 15, 411–418 (2008).

    Google Scholar 

  21. Den Blaauwen, T., Lindqvist, A., Löwe, J. & Nanninga, N. Distribution of the Escherichia coli structural maintenance of chromosomes (SMC)-like protein MukB in the cell. Mol. Microbiol. 42, 1179–1188 (2001).

    Google Scholar 

  22. Ohsumi, K., Yamazoe, M. & Hiraga, S. Different localization of SeqA-bound nascent DNA clusters and MukF-MukE-MukB complex in Escherichia coli cells. Mol. Microbiol. 40, 835–845 (2001).

    Google Scholar 

  23. She, W., Wang, Q., Mordukhova, E. A. & Rybenkov, V. V. MukEF is required for stable association of MukB with the chromosome. J. Bacteriol. 189, 7062–7068 (2007).

    Google Scholar 

  24. Badrinarayanan, A., Lesterlin, C., Reyes-Lamothe, R. & Sherratt, D. J. The Escherichia coli SMC complex, MukBEF, shapes nucleoid organization independently of DNA replication. J. Bacteriol. 194, 4669–4676 (2012).

    Google Scholar 

  25. Badrinarayanan, A., Reyes-Lamothe, R., Uphoff, S., Leake, M. C. & Sherratt, D. J. In vivo architecture and action of bacterial structural maintenance of chromosome proteins. Science 338, 528–531 (2012).

    ADS  Google Scholar 

  26. Nolivos, S. et al. MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation. Nat. Commun. 7, 10466 (2016).

    ADS  Google Scholar 

  27. Ietswaart, R., Szardenings, F., Gerdes, K. & Howard, M. Competing ParA structures space bacterial plasmids equally over the nucleoid. PLoS Comput. Biol. 10, e1004009 (2014).

    ADS  Google Scholar 

  28. Wang, H., Wingreen, N. S. & Mukhopadhyay, R. Self-organized periodicity of protein clusters in growing bacteria. Phys. Rev. Lett. 101, 218101 (2008).

    ADS  Google Scholar 

  29. Petrushenko, Z. M., Lai, C.-H. & Rybenkov, V. V. Antagonistic interactions of kleisins and DNA with bacterial Condensin MukB. J. Biol. Chem. 281, 34208–34217 (2006).

    Google Scholar 

  30. Crampin, E. J., Gaffney, E. A. & Maini, P. K. Reaction and diffusion on growing domains: scenarios for robust pattern formation. Bull. Math. Biol. 61, 1093–1120 (1999).

    MATH  Google Scholar 

  31. Willemse, J., Borst, J. W., de Waal, E., Bisseling, T. & van Wezel, G. P. Positive control of cell division: FtsZ is recruited by SsgB during sporulation of Streptomyces. Genes Dev. 25, 89–99 (2011).

    Google Scholar 

  32. Danilova, O., Reyes-Lamothe, R., Pinskaya, M., Sherratt, D. J. & Possoz, C. MukB colocalizes with the oriC region and is required for organization of the two Escherichia coli chromosome arms into separate cell halves. Mol. Microbiol. 65, 1485–1492 (2007).

    Google Scholar 

  33. Nicolas, E. et al. The SMC complex MukBEF recruits topoisomerase IV to the origin of replication region in live Escherichia coli. MBio 5, e01001-13 (2014).

    Google Scholar 

  34. Wang, X., Possoz, C. & Sherratt, D. J. Dancing around the divisome: asymmetric chromosome segregation in Escherichia coli. Genes Dev. 19, 2367–2377 (2005).

    Google Scholar 

  35. Fisher, J. K. et al. Four-dimensional imaging of E. coli nucleoid organization and dynamics in living cells. Cell 153, 882–895 (2013).

    Google Scholar 

  36. Gruber, S. & Errington, J. Recruitment of condensin to replication origin regions by ParB/SpoOJ promotes chromosome segregation in B. subtilis. Cell 137, 685–696 (2009).

    Google Scholar 

  37. Minnen, A. et al. Control of Smc coiled coil architecture by the ATPase heads facilitates targeting to chromosomal ParB/parS and release onto flanking DNA. Cell Rep. 14, 2003–2016 (2016).

    Google Scholar 

  38. Sullivan, N. L., Marquis, K. A. & Rudner, D. Z. Recruitment of SMC by ParB-parS organizes the origin region and promotes efficient chromosome segregation. Cell 137, 697–707 (2009).

    Google Scholar 

  39. Wang, X., Liu, X., Possoz, C. & Sherratt, D. J. The two Escherichia coli chromosome arms locate to separate cell halves. Genes Dev. 20, 1727–1731 (2006).

    Google Scholar 

  40. Bates, D. & Kleckner, N. Chromosome and replisome dynamics in E. coli: loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation. Cell 121, 899–911 (2005).

    Google Scholar 

  41. Nielsen, H. J., Li, Y., Youngren, B., Hansen, F. G. & Austin, S. Progressive segregation of the Escherichia coli chromosome. Mol. Microbiol. 61, 383–393 (2006).

    Google Scholar 

  42. Lau, I. F. et al. Spatial and temporal organization of replicating Escherichia coli chromosomes. Mol. Microbiol. 49, 731–743 (2004).

    Google Scholar 

  43. Lim, H. C. et al. Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation. eLife 2014, e02758 (2014).

    Google Scholar 

  44. Hu, L., Vecchiarelli, A. G., Mizuuchi, K., Neuman, K. C. & Liu, J. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system. Proc. Natl Acad. Sci. USA 112, E7055–E7064 (2015).

    ADS  Google Scholar 

  45. Halley, J. D. & Winkler, D. A. Consistent concepts of self-organization and self-assembly. Complexity 14, 10–17 (2008).

    Google Scholar 

  46. Roberts, M. A. J., Wadhams, G. H., Hadfield, K. A., Tickner, S. & Armitage, J. P. ParA-like protein uses nonspecific chromosomal DNA binding to partition protein complexes. Proc. Natl Acad. Sci. USA 109, 6698–6703 (2012).

    ADS  Google Scholar 

  47. Treuner-Lange, A. et al. PomZ, a ParA-like protein, regulates Z-ring formation and cell division in Myxococcus xanthus. Mol. Microbiol. 87, 235–253 (2013).

    Google Scholar 

  48. Dillon, R., Maini, P. K. & Othmer, H. G. Pattern formation in generalized Turing systems. J. Math. Biol. 32, 345–393 (1994).

    MathSciNet  MATH  Google Scholar 

  49. Matoba, K., Yamazoe, M., Mayanagi, K., Morikawa, K. & Hiraga, S. Comparison of MukB homodimer versus MukBEF complex molecular architectures by electron microscopy reveals a higher-order multimerization. Biochem. Biophys. Res. Commun. 333, 694–702 (2005).

    Google Scholar 

  50. Gloyd, M., Ghirlando, R. & Guarné, A. The role of MukE in assembling a functional MukBEF complex. J. Mol. Biol. 412, 578–590 (2011).

    Google Scholar 

  51. Crampin, E. J. & Maini, P. K. Reaction-diffusion models for biological pattern formation. Methods Appl. Anal. 8, 415–428 (2001).

    MathSciNet  MATH  Google Scholar 

  52. Gillespie, D. T. Stochastic simulation of chemical kinetics. Annu. Rev. Phys. Chem. 58, 35–55 (2007).

    ADS  Google Scholar 

  53. Gibson, M. & Bruck, J. Efficient exact stochastic simulation of chemical systems with many species and many channels. J. Phys. Chem. A 104, 1876–1889 (2000).

    Google Scholar 

  54. Cao, Y., Li, H. & Petzold, L. R. Efficient formulation of the stochastic simulation algorithm for chemically reacting systems. J. Chem. Phys. 121, 4059–4067 (2004).

    ADS  Google Scholar 

  55. Riaz, S. S., Sharma, R., Bhattacharyya, S. P. & Ray, D. S. Instability and pattern formation in reaction-diffusion systems: a higher order analysis. J. Chem. Phys. 127, 64503 (2007).

    Google Scholar 

  56. Wei, J. & Winter, M. Mathematical Aspects of Pattern Formation in Biological Systems. Applied Mathematical Sciences Vol. 189 (Springer, 2014).

    MATH  Google Scholar 

  57. Bakshi, S. et al. Nonperturbative imaging of nucleoid morphology in live bacterial cells during an antimicrobial peptide attack. Appl. Environ. Microbiol. 80, 4977–4986 (2014).

    Google Scholar 

  58. Sliusarenko, O., Heinritz, J., Emonet, T. & Jacobs-Wagner, C. High-throughput, subpixel precision analysis of bacterial morphogenesis and intracellular spatio-temporal dynamics. Mol. Microbiol. 80, 612–627 (2011).

    Google Scholar 

  59. Wallden, M., Fange, D., Lundius, E. G., Baltekin, Ö & Elf, J. The synchronization of replication and division cycles in individual E. coli cells. Cell 166, 729–739 (2016).

    Google Scholar 

Download references

Acknowledgements

We thank D. Sherratt for providing strain AB45 and R. Colin, U. Endesfelder, P. Graumann, M. Howard, S. Jun and A. Paulick for discussions and/or comments on the manuscript. This work was supported by the German Federal Ministry of Education and Research and the Max Planck Society in the framework of the research network MaxSynBio.

Author information

Authors and Affiliations

  1. Max Planck Institute for Terrestrial Microbiology & LOEWE Centre for Synthetic Microbiology (SYNMIKRO), Karl-von-Frisch Strasse 16, 35043 Marburg, Germany

    Seán M. Murray & Victor Sourjik

Authors
  1. Seán M. Murray
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victor Sourjik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.M.M. initiated the work, conceived the model and designed and performed simulations and experiments. V.S. contributed to experiment design. Both authors discussed the results and implications. S.M.M. wrote the initial draft of the manuscript. Both authors edited subsequent and final versions of the manuscript.

Corresponding author

Correspondence to Seán M. Murray.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 1973 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Murray, S., Sourjik, V. Self-organization and positioning of bacterial protein clusters. Nature Phys 13, 1006–1013 (2017). https://doi.org/10.1038/nphys4155

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nphys4155

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing