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:

Membrane-induced bundling of actin filaments

Nature Physics volume 4, pages 789–793 (2008)Cite this article

Abstract

Dynamic interplay between the plasma membrane and underlying cytoskeleton is essential for cellular shape change. Spatial organization of actin filaments, the growth of which generates membrane deformations during motility1, phagocytosis2, endocytosis3 and cytokinesis4, is mediated by specific protein–protein interactions that branch, crosslink and bundle filaments into networks that interact with the membrane. Although membrane curvature has been found to influence binding of proteins with curvature-sensitive domains5, the direct effect of membrane elasticity on cytoskeletal network organization is not clear. Here, we show through in vitro reconstitution and elastic modelling that a lipid bilayer can drive the emergence of bundled actin filament protrusions from branched actin filament networks, thus playing a role normally attributed to actin-binding proteins. Formation of these filopodium-like protrusions with only a minimal set of purified proteins points to an active participation of the membrane in organizing actin filaments at the plasma membrane. In this way, elastic interactions between the membrane and cytoskeleton can cooperate with accessory proteins to drive cellular shape change.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Figure 1: Thin actin protrusions emerge from dendritic actin networks.
Figure 2: Elongation of a thin actin filament protrusion by polymerization proximal to the membrane.
Figure 3: Role of membrane in formation of thin actin filament protrusions.

Similar content being viewed by others

References

  1. Pollard, T. D. & Borisy, G. G. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112, 453–465 (2003).

    Article  Google Scholar 

  2. Yeung, T., Ozdamar, B., Paroutis, P. & Grinstein, S. Lipid metabolism and dynamics during phagocytosis. Curr. Opin. Cell Biol. 18, 429–437 (2006).

    Article  Google Scholar 

  3. Smythe, E. & Ayscough, K. R. Actin regulation in endocytosis. J. Cell Sci. 119, 4589–4598 (2006).

    Article  Google Scholar 

  4. Eggert, U. S., Mitchison, T. J. & Field, C. M. Animal cytokinesis: From parts list to mechanisms. Annu. Rev. Biochem. 75, 543–566 (2006).

    Article  Google Scholar 

  5. McMahon, H. T. & Gallop, J. L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 438, 590–596 (2005).

    Article  ADS  Google Scholar 

  6. Mullins, R. D., Heuser, J. A. & Pollard, T. D. The interaction of Arp2/3 complex with actin: Nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc. Natl Acad. Sci. USA 95, 6181–6186 (1998).

    Article  ADS  Google Scholar 

  7. Loisel, T. P., Boujemaa, R., Pantaloni, D. & Carlier, M. F. Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature 401, 613–616 (1999).

    Article  ADS  Google Scholar 

  8. Bernheim-Groswasser, A., Wiesner, S., Golsteyn, R. M., Carlier, M. F. & Sykes, C. The dynamics of actin-based motility depend on surface parameters. Nature 417, 308–311 (2002).

    Article  ADS  Google Scholar 

  9. Giardini, P. A., Fletcher, D. A. & Theriot, J. A. Compression forces generated by actin comet tails on lipid vesicles. Proc. Natl Acad. Sci. USA 100, 6493–6498 (2003).

    Article  ADS  Google Scholar 

  10. Upadhyaya, A., Chabot, J. R., Andreeva, A., Samadani, A. & van Oudenaarden, A. Probing polymerization forces by using actin-propelled lipid vesicles. Proc. Natl Acad. Sci. USA 100, 4521–4526 (2003).

    Article  ADS  Google Scholar 

  11. Liu, A. P. & Fletcher, D. A. Actin polymerization serves as a membrane domain switch in model lipid bilayers. Biophys. J. 91, 4064–4070 (2006).

    Article  ADS  Google Scholar 

  12. Co, C., Wong, D. T., Gierke, S., Chang, V. & Taunton, J. Mechanism of actin network attachment to moving membranes: Barbed end capture by N-WASP WH2 domains. Cell 128, 901–913 (2007).

    Article  Google Scholar 

  13. Mogilner, A. & Rubinstein, B. The physics of filopodial protrusion. Biophys. J. 89, 782–795 (2005).

    Article  Google Scholar 

  14. Svitkina, T. M. et al. Mechanism of filopodia initiation by reorganization of a dendritic network. J. Cell Biol. 160, 409–421 (2003).

    Article  Google Scholar 

  15. Faix, J. & Rottner, K. The making of filopodia. Curr. Opin. Cell Biol. 18, 18–25 (2006).

    Article  Google Scholar 

  16. Atilgan, E., Wirtz, D. & Sun, S. X. Mechanics and dynamics of actin-driven thin membrane protrusions. Biophys. J. 90, 65–76 (2006).

    Article  ADS  Google Scholar 

  17. Derenyi, I., Julicher, F. & Prost, J. Formation and interaction of membrane tubes. Phys. Rev. Lett. 88, 238101 (2002).

    Article  ADS  Google Scholar 

  18. Pronk, S., Geissler, P. L. & Fletcher, D. A. Limits of filopodium stability. Phys. Rev. Lett. 100, 258102 (2008).

    Article  ADS  Google Scholar 

  19. Wood, W. et al. Wound healing recapitulates morphogenesis in Drosophila embryos. Nature Cell Biol. 4, 907–912 (2002).

    Article  Google Scholar 

  20. Onfelt, B. et al. Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria. J. Immunol. 177, 8476–8483 (2006).

    Article  Google Scholar 

  21. Fygenson, D. K., Elbaum, M., Shraiman, B. & Libchaber, A. Microtubules and vesicles under controlled tension. Phys. Rev. E 55, 850–859 (1997).

    Article  ADS  Google Scholar 

  22. Sigal, Y. J., Quintero, O. A., Cheney, R. E. & Morris, A. J. Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane lipid-phosphatase-related protein. J. Cell Sci. 120, 340–352 (2007).

    Article  Google Scholar 

  23. Mattila, P. K. et al. Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism. J. Cell Biol. 176, 953–964 (2007).

    Article  Google Scholar 

  24. Snapper, S. B. et al. N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility. Nature Cell Biol. 3, 897–904 (2001).

    Article  Google Scholar 

  25. Steffen, A. et al. Filopodia formation in the absence of functional WAVE- and Arp2/3-complexes. Mol. Biol. Cell 17, 2581–2591 (2006).

    Article  Google Scholar 

  26. Gupton, S. L. & Gertler, F. B. Filopodia: The fingers that do the walking. Sci. STKE 2007, re5 (2007).

    Article  Google Scholar 

  27. Spudich, J. A. & Watt, S. The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin. J. Biol. Chem. 246, 4866–4871 (1971).

    Google Scholar 

  28. Papayannopoulos, V. et al. A polybasic motif allows N-WASP to act as a sensor of PIP(2) density. Mol. Cell 17, 181–191 (2005).

    Article  Google Scholar 

  29. Egile, C. et al. Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility. J. Cell Biol. 146, 1319–1332 (1999).

    Article  Google Scholar 

  30. Wiesner, S. et al. A biomimetic motility assay provides insight into the mechanism of actin-based motility. J. Cell Biol. 160, 387–398 (2003).

    Article  Google Scholar 

Download references

Acknowledgements

We thank D. Drubin and E. Nogales, as well as M. van Duijn, R. Rounsvell, S. Parekh and other members of the Fletcher laboratory for helpful discussions. We thank V. Risca for her help with confocal microscopy, and J. Taunton, D. Wong and C. Co for providing various proteins. We are grateful to C. Fromme for assisting us with fast protein liquid chromatography. This work is supported in part by a fellowship from the Natural Sciences and Engineering Research Council of Canada (A.P.L. and D.L.R.) and by funding from the NIH for the Cell Propulsion Laboratory as part of the Nanomedicine Roadmap Initiative (D.A.F.).

Author information

Author notes

  1. Allen P. Liu and David L. Richmond: These authors contributed equally to this work

Authors and Affiliations

  1. Graduate Group in Biophysics, University of California at Berkeley, Berkeley, California 94720, USA

    Allen P. Liu, David L. Richmond, Phillip L. Geissler & Daniel A. Fletcher

  2. Department of Chemistry, University of California at Berkeley, Berkeley, California 94720, USA

    Lutz Maibaum & Phillip L. Geissler

  3. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

    Lutz Maibaum, Phillip L. Geissler & Daniel A. Fletcher

  4. Department of Bioengineering, University of California at Berkeley, Berkeley, California 94720, USA

    Sander Pronk & Daniel A. Fletcher

  5. Chemical Sciences and Material Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA

    Phillip L. Geissler

Authors
  1. Allen P. Liu
    View author publications

    Search author on:PubMed Google Scholar

  2. David L. Richmond
    View author publications

    Search author on:PubMed Google Scholar

  3. Lutz Maibaum
    View author publications

    Search author on:PubMed Google Scholar

  4. Sander Pronk
    View author publications

    Search author on:PubMed Google Scholar

  5. Phillip L. Geissler
    View author publications

    Search author on:PubMed Google Scholar

  6. Daniel A. Fletcher
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Daniel A. Fletcher.

Supplementary information

Supplementary Information

Supplementary Notes and Supplementary Figures 1–7 (PDF 306 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, A., Richmond, D., Maibaum, L. et al. Membrane-induced bundling of actin filaments. Nature Phys 4, 789–793 (2008). https://doi.org/10.1038/nphys1071

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nphys1071

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