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Inferring transient particle transport dynamics in live cells

Nature Methods volume 12, pages 838840 (2015) | Download Citation

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/.

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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

    • Nilah Monnier
    • , Hye Yoon Park
    • , Zachary Katz
    •  & Arkajit Dey

    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.).

    • Nilah Monnier
    •  & Zachary Barry

    These authors contributed equally to this work.

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

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Mark Bathe.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–27, Supplementary Table 1 and Supplementary Notes 1–7

Videos

  1. 1.

    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.

  2. 2.

    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.

  3. 3.

    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.

Zip files

  1. 1.

    Supplementary Software

    HMM-Bayes analysis package and associated documentation.

About this article

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DOI

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

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