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.

Inferring transient particle transport dynamics in live cells

Nature Methods volume 12, pages 838–840 (2015)Cite this article

Subjects

Abstract

Live-cell imaging and particle tracking provide rich information on mechanisms of intracellular transport. However, trajectory analysis procedures to infer complex transport dynamics involving stochastic switching between active transport and diffusive motion are lacking. We applied Bayesian model selection to hidden Markov modeling to infer transient transport states from trajectories of mRNA-protein complexes in live mouse hippocampal neurons and metaphase kinetochores in dividing human cells. The software is available at http://hmm-bayes.org/.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Particle-trajectory analysis methods applied to neuronal mRNPs.
Figure 2: HMM-Bayes analysis of neuronal mRNPs.
Figure 3: HMM-Bayes analysis of oscillating metaphase kinetochores.

References

  1. Saxton, M.J. & Jacobson, K. Annu. Rev. Biophys. Biomol. Struct. 26, 373–399 (1997).

    CAS  Article  Google Scholar 

  2. Chung, I. et al. Nature 464, 783–787 (2010).

    CAS  Article  Google Scholar 

  3. Jaqaman, K. et al. Cell 146, 593–606 (2011).

    CAS  Article  Google Scholar 

  4. Lionnet, T. et al. Nat. Methods 8, 165–170 (2011).

    CAS  Article  Google Scholar 

  5. Park, H.Y. et al. Science 343, 422–424 (2014).

    CAS  Article  Google Scholar 

  6. Vladimirou, E. et al. Dev. Cell 27, 60–71 (2013).

    CAS  Article  Google Scholar 

  7. Jaqaman, K. et al. Nat. Methods 5, 695–702 (2008).

    CAS  Article  Google Scholar 

  8. Chenouard, N. et al. Nat. Methods 11, 281–289 (2014).

    CAS  Article  Google Scholar 

  9. Saxton, M.J. Nat. Methods 11, 247–248 (2014).

    CAS  Article  Google Scholar 

  10. Monnier, N. et al. Biophys. J. 103, 616–626 (2012).

    CAS  Article  Google Scholar 

  11. Das, R., Cairo, C.W. & Coombs, D. PLoS Comput. Biol. 5, e1000556 (2009).

    Article  Google Scholar 

  12. Cairo, C.W. et al. J. Biol. Chem. 285, 11392–11401 (2010).

    CAS  Article  Google Scholar 

  13. Persson, F., Lindén, M., Unoson, C. & Elf, J. Nat. Methods 10, 265–269 (2013).

    Article  Google Scholar 

  14. Arcizet, D., Meier, B., Sackmann, E., Rädler, J.O. & Heinrich, D. Phys. Rev. Lett. 101, 248103 (2008).

    Article  Google Scholar 

  15. Katz, Z.B. et al. Genes Dev. 26, 1885–1890 (2012).

    CAS  Article  Google Scholar 

  16. Cheeseman, I.M. & Desai, A. Nat. Rev. Mol. Cell Biol. 9, 33–46 (2008).

    CAS  Article  Google Scholar 

  17. Deforet, M. et al. Nat. Methods 9, 1081–1083 (2012).

    CAS  Article  Google Scholar 

  18. Tomer, R., Khairy, K., Amat, F. & Keller, P.J. Nat. Methods 9, 755–763 (2012).

    CAS  Article  Google Scholar 

  19. Dray, N. et al. Curr. Biol. 23, 1335–1341 (2013).

    CAS  Article  Google Scholar 

  20. Saxton, M.J. Biophys. J. 64, 1766–1780 (1993).

    CAS  Article  Google Scholar 

  21. Ewens, W.J. & Grant, G.R. Statistical Methods in Bioinformatics (Springer, 2005).

  22. Robert, C.P. & Casella, G. Monte Carlo Statistical Methods (Springer, 2004).

  23. Grimmett, G. & Stirzaker, D. Probability and Random Processes 3rd edn. (Oxford University Press, 2001).

  24. Gilks, W.R., Richardson, S. & Spiegelhalter, D.J. Markov Chain Monte Carlo in Practice (Chapman & Hall/CRC, 1996).

  25. Gelman, A., Gilks, W.R. & Roberts, G.O. Ann. Appl. Probab. 7, 110–120 (1997).

    Article  Google Scholar 

  26. He, J., Guo, S.M. & Bathe, M. Anal. Chem. 84, 3871–3879 (2012).

    CAS  Article  Google Scholar 

  27. Vallotton, P. & Olivier, S. Microsc. Microanal. 19, 451–460 (2013).

    CAS  Article  Google Scholar 

  28. Backer, C.B., Gutzman, J.H., Pearson, C.G. & Cheeseman, I.M. Mol. Biol. Cell 23, 2122–2130 (2012).

    CAS  Article  Google Scholar 

  29. Gascoigne, K.E. et al. Cell 145, 410–422 (2011).

    CAS  Article  Google Scholar 

  30. Meijering, E., Dzyubachyk, O. & Smal, I. Methods Enzymol. 504, 183–200 (2012).

    Article  Google Scholar 

Download references

Acknowledgements

Research reported in this publication was supported by grants from the US National Institutes of Health (NIH) National Institute of Mental Health (U01 MH106011) and the US National Science Foundation Physics of Living Systems (PHY 1305537) to M.B., an NIH grant from the National Institute of Neurological Diseases and Stroke (NS083085-19) to R.H.S., a Scholar award from the Leukemia & Lymphoma Society and an NIH grant from the National Institute of General Medical Sciences (GM088313) to I.M.C., and a Schroedinger fellowship from the Austrian Science Fund to K.-C.S. We also thank M. Linden for helpful discussions.

Author information

Author notes

  1. Nilah Monnier, Hye Yoon Park, Zachary Katz & Arkajit Dey

    Present address: Present addresses: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA (N.M.); Department of Physics and Astronomy, Seoul National University, Seoul, South Korea (H.Y.P.); Salk Institute for Biological Studies, La Jolla, California, USA (Z.K.); Twitter Inc., San Francisco, California, USA (A.D.).,

  2. Nilah Monnier and Zachary Barry: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Nilah Monnier, Zachary Barry, Arkajit Dey, Keyao Pan & Mark Bathe

  2. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA

    Hye Yoon Park, Zachary Katz & Robert H Singer

  3. Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA

    Hye Yoon Park & Robert H Singer

  4. Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, Virginia, USA

    Hye Yoon Park, Brian P English & Robert H Singer

  5. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA

    Kuan-Chung Su & Iain M Cheeseman

  6. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Kuan-Chung Su & Iain M Cheeseman

Authors
  1. Nilah Monnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zachary Barry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hye Yoon Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kuan-Chung Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zachary Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Brian P English
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arkajit Dey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Keyao Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Iain M Cheeseman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Robert H Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mark Bathe
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

N.M. and M.B. conceived the method; N.M., A.D., K.P. and M.B. developed the theory; N.M. and Z.B. implemented the method; H.Y.P., Z.K., B.P.E. and R.H.S. collected mRNP data sets and advised on their analysis; K.-C.S. and I.M.C. collected kinetochore data sets and advised on their analysis; Z.B. and N.M. analyzed experimental data sets; N.M., Z.B. and M.B. wrote the paper.

Corresponding author

Correspondence to Mark Bathe.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–27, Supplementary Table 1 and Supplementary Notes 1–7 (PDF 8120 kb)

Motion of neuronal mRNP #1 from Fig. 1

Raw fluorescence images of the mRNP from Fig. 1 in a live neuron. The left panel also shows the tracked particle positions (pink circles) and the resulting trajectory annotated with HMM-Bayes as in Fig. 1d. (AVI 1226 kb)

Motion of neuronal mRNP #2 from Fig. 2a

Raw fluorescence images of the mRNP from Fig. 2a in a live neuron. The left panel also shows the tracked particle positions (pink circles) and the resulting trajectory annotated with HMM-Bayes as in Fig. 2a. (AVI 4225 kb)

Motion of neuronal mRNP #3 from Fig. 2b

Raw fluorescence images of the mRNP from Fig. 2b in a live neuron. The left panel also shows the tracked particle positions (pink circles) and the resulting trajectory annotated with HMM-Bayes as in Fig. 2b. (AVI 5417 kb)

Supplementary Software

HMM-Bayes analysis package and associated documentation. (ZIP 10511 kb)

Source data

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Monnier, N., Barry, Z., Park, H. et al. Inferring transient particle transport dynamics in live cells. Nat Methods 12, 838–840 (2015). https://doi.org/10.1038/nmeth.3483

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth.3483

Further reading

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