The dynamics of actin-based motility depend on surface parameters

Abstract

In cells, actin polymerization at the plasma membrane is induced by the recruitment of proteins such as the Arp2/3 complex, and the zyxin/VASP complex1,2,3. The physical mechanism of force generation by actin polymerization has been described theoretically using various approaches4,5,6, but lacks support from experimental data. By the use of reconstituted motility medium7, we find that the Wiskott–Aldrich syndrome protein8,9 (WASP) subdomain, known as VCA, is sufficient to induce actin polymerization and movement when grafted on microspheres. Changes in the surface density of VCA protein or in the microsphere diameter markedly affect the velocity regime, shifting from a continuous to a jerky movement resembling that of the mutated ‘hopping’ Listeria10. These results highlight how simple physical parameters such as surface geometry and protein density directly affect spatially controlled actin polymerization, and play a fundamental role in actin-dependent movement.

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Figure 1: The three main regimes of motion of the beads as a function of bead diameter.
Figure 2: The characteristic behaviour of a 4.5-µm bead at a saturated VCA surface density Cs.
Figure 3: The linear dependence between the time of symmetry breaking and the bead diameter.

References

  1. 1

    Welch, M. D., Mallavarapu, A., Rosenblatt, J. & Mitchison, T. J. Actin dynamics in vivo. Curr. Opin. Cell. Biol. 9, 54–61 (1997)

    CAS  Article  PubMed  Google Scholar 

  2. 2

    Renfranz, P. J. & Beckerle, M. C. Doing (F/L)PPPPS: EVH1 domains and their proline-rich partners in cell polarity and migration. Curr. Opin. Cell Biol. 14, 88–103 (2002)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3

    Pantaloni, D., Le Clainche, C. & Carlier, M.-F. Mechanism of actin-based motility. Science 292, 1502–1506 (2001)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4

    Mogilner, A. & Oster, G. Cell motility driven by actin polymerisation. Biophys. J. 71, 3030–3045 (1996)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5

    Gerbal, F., Chaikin, P., Rabin, Y. & Prost, J. An elastic analysis of Listeria monocytogenes propulsion. Biophys. J. 79, 2259–2275 (2000)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Carlsson, A. E. Growth of branched actin networks against obstacles. Biophys. J. 81, 1907–1923 (2001)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 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)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Machesky, L. M. & Insall, R. H. Scar1 and the related Wiskott–Aldrich syndrome protein, WASP regulates the actin cytoskeleton through the Arp2/3 complex. Curr. Biol. 8, 1347–1356 (1998)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9

    Takenawa, T. & Miki, H. WASp and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci. 114, 1801–1809 (2001)

    CAS  Google Scholar 

  10. 10

    Lasa, I. et al. Identification of two regions in the N-terminal domain of ActA involved in the actin comet tail formation by Listeria monocytogenes. EMBO J. 16, 1531–1540 (1997)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11

    Tilney, L. G. & Portnoy, D. A. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J. Cell Biol. 109, 1597–1608 (1989)

    CAS  Article  PubMed  Google Scholar 

  12. 12

    Welch, M. D., Iwamatsu, A. & Mitchison, T. J. Actin polymerisation is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 385, 265–268 (1997)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Egile, C. et al. Activation of Cdc42 effector N-WASP by the Shigella IcsA protein promotes actin nucleation by Arp2/3 complex resulting in bacterial actin-based motility. J. Cell. Biol. 146, 1319–1332 (1999)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Svitkina, T. M. & Borisy, G. G. Arp2/3 complex and actin polymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 145, 1009–1026 (1999)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15

    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)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Blanchoin, L. et al. Direct observation of dendritic actin filaments networks nucleated by Arp2/3 complex and WASP/Scar proteins. Nature 404, 1007–1011 (2000)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Pantaloni, D., Boujemaa, R., Didry, D., Gounon, P. & Carlier, M.-F. The Arp2/3 complex branches filament barbed ends: functional antagonism with capping proteins. Nature Cell Biol. 2, 385–391 (2000)

    CAS  Article  Google Scholar 

  18. 18

    Fradelizi, J. et al. ActA and human zyxin harbour Arp2/3-independent actin-polymerisation activity. Nature Cell Biol. 3, 699–707 (2001)

    CAS  Article  PubMed  Google Scholar 

  19. 19

    Cameron, L. A., Svitkina, T. M., Vignjevic, D., Theriot, J. A. & Borisy, G. G. Dendritic organization of actin comet tails. Curr. Biol. 11, 130–135 (2001)

    CAS  Article  PubMed  Google Scholar 

  20. 20

    Cameron, L. A., Footer, M. J., van Oudenaarden, A. & Theriot, J. A. Motility of ActA protein-coated microspheres driven by actin polymerisation. Proc. Natl Acad. Sci. USA 96, 4908–4913 (1999)

    ADS  CAS  Article  PubMed  Google Scholar 

  21. 21

    Noireaux, V. et al. Growing an actin gel on spherical surfaces. Biophys. J. 78, 1643–1654 (2000)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22

    Giardini, P. A. & Theriot, J. A. Effects of intermediate filaments on actin-based motility of Listeria monocytogenes. Biophys. J. 81, 3193–3203 (2001)

    ADS  CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23

    Gerbal, F. et al. On the ‘Listeria’ propulsion mechanism. Pramana J. Phys. 53, 155–170 (1999)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Kuo, S. C. & McGrath, L. Steps and fluctuations of Listeria monocytogenes during actin-based motility. Nature 407, 1026–1029 (2000)

    ADS  CAS  Article  PubMed  Google Scholar 

  25. 25

    Rutenberg, A. D. & Grant, M. Curved tails in polymerization-based bacterial motility. Phys. Rev. E 64, 21904–21907 (2001)

    ADS  CAS  Article  Google Scholar 

  26. 26

    Merrifield, C. J. et al. Endocytic vesicles move at the tips of actin tails in cultured mast cells. Nature Cell Biol. 1, 72–74 (1999)

    CAS  Article  Google Scholar 

  27. 27

    Taunton, J. et al. Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP. J. Cell Biol. 148, 519–530 (2000)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. 28

    Van Oudenaarden, A. & Theriot, J. A. Cooperative symmetry-breaking by actin polymerisation in a model for cell motility. Nature Cell Biol. 1, 493–499 (1999)

    CAS  Article  PubMed  Google Scholar 

  29. 29

    Beningo, K. A., Dembo, M., Kaverina, I., Small, J. V. & Wang, Y. Nascentfocal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 89–100 (2001)

    Article  Google Scholar 

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Acknowledgements

We thank J. Plastino for discussions and the purification of VCA proteins, and F. Castellano and P. Chavrier for the gift of the plasmid encoding VCA. Theoretical discussions were conducted by J. Prost. We thank D. Didry for the purification of Arp2/3, ADF-cofilin, and actin, and R. Boujemaa for the purification of the capping protein. We thank H. Boukellal for help in determining the VCA concentration on the beads, E. Paluch for helping in analysing the videos and K. Sekimoto and D. Pantaloni for discussions.

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Correspondence to Marie-France Carlier or Cécile Sykes.

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Bernheim-Groswasser, A., Wiesner, S., Golsteyn, R. et al. The dynamics of actin-based motility depend on surface parameters. Nature 417, 308–311 (2002). https://doi.org/10.1038/417308a

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