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.

  • Letter
  • Published:

Memoryless self-reinforcing directionality in endosomal active transport within living cells

Subjects

Abstract

In contrast to Brownian transport, the active motility of microbes, cells, animals and even humans often follows another random process known as truncated Lévy walk1,2. These stochastic motions are characterized by clustered small steps and intermittent longer jumps that often extend towards the size of the entire system. As there are repeated suggestions, although disagreement, that Lévy walks have functional advantages over Brownian motion in random searching and transport kinetics3,4,5,6,7,8, their intentional engineering into active materials could be useful. Here, we show experimentally in the classic active matter system of intracellular trafficking9,10,11,12,13,14,15 that Brownian-like steps self-organize into truncated Lévy walks through an apparent time-independent positive feedback such that directional persistence increases with the distance travelled persistently. A molecular model that allows the maximum output of the active propelling forces to fluctuate slowly fits the experiments quantitatively. Our findings offer design principles for programming efficient transport in active materials.

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

Access options

Buy this article

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

Figure 1: Feedback in directional persistence transforms transport dynamics.
Figure 2: Trajectories of endosomes in live cells.
Figure 3: Combined experiments and numerical modelling show that positive feedback in directional persistence during intracellular trafficking transforms Brownian-like steps to truncated Lévy walks.
Figure 4: The balance of competing factors determines feedback and the nature of the transport dynamics.

Similar content being viewed by others

References

  1. Shlesinger, M. F., Zaslavsky, G. M. & Klafter, J. Strange kinetics. Nature 363, 31–37 (1993).

    Article  CAS  Google Scholar 

  2. Mantegna, R. N. & Stanley, H. E. Stochastic-process with ultraslow convergence to a Gaussian: The truncated Lévy flight. Phys. Rev. Lett. 73, 2946–2949 (1994).

    Article  CAS  Google Scholar 

  3. Viswanathan, G. M. et al. Optimizing the success of random searches. Nature 401, 911–914 (1999).

    Article  CAS  Google Scholar 

  4. Palyulin, V. V., Chechkin, A. V. & Metzler, R. Lévy flights do not always optimize random blind search for sparse targets. Proc. Natl Acad. Sci. USA 111, 2931–2936 (2014).

    Article  CAS  Google Scholar 

  5. Bartumeus, F., Peters, F., Pueyo, S., Marrase, C. & Catalan, J. Helical Lévy walks: Adjusting searching statistics to resource availability in microzooplankton. Proc. Natl Acad. Sci. USA 100, 12771–12775 (2003).

    Article  CAS  Google Scholar 

  6. Barthelemy, P., Bertolotti, J. & Wiersma, D. S. A Lévy flight for light. Nature 453, 495–498 (2008).

    Article  CAS  Google Scholar 

  7. De Jager, M., Weissing, F. J., Herman, P. M. J., Nolet, B. A. & van de Koppel, J. Lévy walks evolve through interaction between movement and environmental complexity. Science 332, 1551–1553 (2011).

    Article  CAS  Google Scholar 

  8. Harris, T. H. et al. Generalized Lévy walks and the role of chemokines in migration of effector CD8(+) T cells. Nature 486, 545–549 (2012).

    Article  CAS  Google Scholar 

  9. Bao, G. & Suresh, S. Cell and molecular mechanics of biological materials. Nature Mater. 2, 715–725 (2003).

    Article  CAS  Google Scholar 

  10. Loverdo, C., Benichou, O., Moreau, M. & Voituriez, R. Enhanced reaction kinetics in biological cells. Nature Phys. 4, 134–137 (2008).

    Article  CAS  Google Scholar 

  11. Wang, B., Kuo, J. & Granick, S. Bursts of active transport in living cells. Phys. Rev. Lett. 111, 208102 (2013).

    Article  Google Scholar 

  12. Trong, P. K., Guck, J. & Goldstein, R. E. Coupling of active motion and advection shapes intracellular cargo transport. Phys. Rev. Lett. 109, 028104 (2012).

    Article  Google Scholar 

  13. Brangwynne, C. P., Koenderink, G. H., MacKintosh, F. C. & Weitz, D. A. Intracellular transport by active diffusion. Trends Cell Biol. 19, 423–427 (2009).

    Article  CAS  Google Scholar 

  14. Tabei, S. M. A. et al. Intracellular transport of insulin granules is a subordinated random walk. Proc. Natl Acad. Sci. USA 110, 4911–4916 (2013).

    Article  Google Scholar 

  15. Fakhri, N. et al. High-resolution mapping of intracellular fluctuations using carbon nanotubes. Science 344, 1031–1035 (2014).

    Article  CAS  Google Scholar 

  16. Bouchaud, J. P. & Georges, A. Anomalous diffusion in disordered media: Statistical mechanisms, models and physical applications. Phys. Rep. 195, 127–293 (1990).

    Article  Google Scholar 

  17. Peterson, J., Dixit, P. D. & Dill, K. A. A maximum entropy framework for nonexponential distributions. Proc. Natl Acad. Sci. USA 110, 20380–20385 (2013).

    Article  CAS  Google Scholar 

  18. Huet, S. et al. Analysis of transient behavior in complex trajectories: Application to secretory vesicle dynamics. Biophys. J. 91, 3542–3559 (2006).

    Article  CAS  Google Scholar 

  19. Arcizet, D., Meier, B., Sackmann, E., Raedler, J. O. & Heinrich, D. Temporal analysis of active and passive transport in living cells. Phys. Rev. Lett. 101, 248103 (2008).

    Article  Google Scholar 

  20. Mueller, M. J. I., Klumpp, S. & Lipowsky, R. Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors. Proc. Natl Acad. Sci. USA 105, 4609–4614 (2008).

    Article  CAS  Google Scholar 

  21. Klumpp, S. & Lipowsky, R. Cooperative cargo transport by several molecular motors. Proc. Natl Acad. Sci. USA 102, 17284–17289 (2005).

    Article  CAS  Google Scholar 

  22. Howard, J. Mechanical signaling in networks of motor and cytoskeletal proteins. Annu. Rev. Biophys. 38, 217–234 (2009).

    Article  CAS  Google Scholar 

  23. Bressloff, P. C. & Newby, J. M. Stochastic models of intracellular transport. Rev. Mod. Phys. 85, 135–196 (2013).

    Article  CAS  Google Scholar 

  24. Reilein, A., Yamada, S. & Nelson, W. J. Self-organization of an acentrosomal microtubule network at the basal cortex of polarized epithelial cells. J. Cell Biol. 171, 845–855 (2005).

    Article  CAS  Google Scholar 

  25. Chen, K., Wang, B., Guan, J. & Granick, S. Diagnosing heterogeneous dynamics in single-molecule/particle trajectories with multiscale wavelets. ACS Nano 7, 8634–8644 (2013).

    Article  CAS  Google Scholar 

  26. Balint, S., Verdeny Vilanova, I., Sandoval Alvarez, A. & Lakadamyali, M. Correlative live-cell and superresolution microscopy reveals cargo transport dynamics at microtubule intersections. Proc. Natl Acad. Sci. USA 110, 3375–3380 (2013).

    Article  CAS  Google Scholar 

  27. Ross, J. L., Ali, M. Y. & Warshaw, D. M. Cargo transport: Molecular motors navigate a complex cytoskeleton. Curr. Opin. Cell Biol. 20, 41–47 (2008).

    Article  CAS  Google Scholar 

  28. Edwards, A. M. et al. Revisiting Lévy flight search patterns of wandering albatrosses, bumblebees and deer. Nature 449, 1044–1048 (2007).

    Article  CAS  Google Scholar 

  29. Herold, C., Leduc, C., Stock, R., Diez, S. & Schwille, P. Long-range transport of giant vesicles along microtubule networks. ChemPhysChem 13, 1001–1006 (2012).

    Article  CAS  Google Scholar 

  30. Vergassola, M., Villermaux, E. & Shraiman, B. I. ‘Infotaxis’ as a strategy for searching without gradients. Nature 445, 406–409 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the US Department of Energy, Division of Materials Science, under Award DEFG02-02ER46019. B.W. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. S.G. acknowledges office support from the Institute for Basic Science, Project Code IBS-R020-D1. We thank J. Kuo and S. C. Bae for experimental help, and J. Cheng for cell culture lab space.

Author information

Authors and Affiliations

Authors

Contributions

K.C. and B.W. developed the analysis; B.W. designed and performed the experiment; K.C., B.W. and S.G. wrote the paper.

Corresponding authors

Correspondence to Bo Wang or Steve Granick.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 788 kb)

Supplementary Movie 1

Supplementary Movie 1 (MOV 4320 kb)

Supplementary Movie 2

Supplementary Movie 2 (MOV 4616 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, K., Wang, B. & Granick, S. Memoryless self-reinforcing directionality in endosomal active transport within living cells. Nature Mater 14, 589–593 (2015). https://doi.org/10.1038/nmat4239

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat4239

This article is cited by

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