Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1996 Dec;71(6):3030–3045. doi: 10.1016/S0006-3495(96)79496-1

Cell motility driven by actin polymerization.

A Mogilner 1, G Oster 1
PMCID: PMC1233792  PMID: 8968574

Abstract

Certain kinds of cellular movements are apparently driven by actin polymerization. Examples include the lamellipodia of spreading and migrating embryonic cells, and the bacterium Listeria monocytogenes, that propels itself through its host's cytoplasm by constructing behind it a polymerized tail of cross-linked actin filaments. Peskin et al. (1993) formulated a model to explain how a polymerizing filament could rectify the Brownian motion of an object so as to produce unidirectional force (Peskin, C., G. Odell, and G. Oster. 1993. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys. J. 65:316-324). Their "Brownian ratchet" model assumed that the filament was stiff and that thermal fluctuations affected only the "load," i.e., the object being pushed. However, under many conditions of biological interest, the thermal fluctuations of the load are insufficient to produce the observed motions. Here we shall show that the thermal motions of the polymerizing filaments can produce a directed force. This "elastic Brownian ratchet" can explain quantitatively the propulsion of Listeria and the protrusive mechanics of lamellipodia. The model also explains how the polymerization process nucleates the orthogonal structure of the actin network in lamellipodia.

Full text

PDF
3030

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bremer A., Millonig R. C., Sütterlin R., Engel A., Pollard T. D., Aebi U. The structural basis for the intrinsic disorder of the actin filament: the "lateral slipping" model. J Cell Biol. 1991 Nov;115(3):689–703. doi: 10.1083/jcb.115.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brundage R. A., Smith G. A., Camilli A., Theriot J. A., Portnoy D. A. Expression and phosphorylation of the Listeria monocytogenes ActA protein in mammalian cells. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11890–11894. doi: 10.1073/pnas.90.24.11890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen Y. T., Holcomb C., Moore H. P. Expression and localization of two low molecular weight GTP-binding proteins, Rab8 and Rab10, by epitope tag. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6508–6512. doi: 10.1073/pnas.90.14.6508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Condeelis J. Are all pseudopods created equal? Cell Motil Cytoskeleton. 1992;22(1):1–6. doi: 10.1002/cm.970220102. [DOI] [PubMed] [Google Scholar]
  5. Condeelis J. Life at the leading edge: the formation of cell protrusions. Annu Rev Cell Biol. 1993;9:411–444. doi: 10.1146/annurev.cb.09.110193.002211. [DOI] [PubMed] [Google Scholar]
  6. Cooper J. A. The role of actin polymerization in cell motility. Annu Rev Physiol. 1991;53:585–605. doi: 10.1146/annurev.ph.53.030191.003101. [DOI] [PubMed] [Google Scholar]
  7. Cramer L. P., Mitchison T. J., Theriot J. A. Actin-dependent motile forces and cell motility. Curr Opin Cell Biol. 1994 Feb;6(1):82–86. doi: 10.1016/0955-0674(94)90120-1. [DOI] [PubMed] [Google Scholar]
  8. Cudmore S., Cossart P., Griffiths G., Way M. Actin-based motility of vaccinia virus. Nature. 1995 Dec 7;378(6557):636–638. doi: 10.1038/378636a0. [DOI] [PubMed] [Google Scholar]
  9. DeBiasio R. L., Wang L. L., Fisher G. W., Taylor D. L. The dynamic distribution of fluorescent analogues of actin and myosin in protrusions at the leading edge of migrating Swiss 3T3 fibroblasts. J Cell Biol. 1988 Dec;107(6 Pt 2):2631–2645. doi: 10.1083/jcb.107.6.2631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dembo M., Harlow F. Cell motion, contractile networks, and the physics of interpenetrating reactive flow. Biophys J. 1986 Jul;50(1):109–121. doi: 10.1016/S0006-3495(86)83444-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dembo M. Mechanics and control of the cytoskeleton in Amoeba proteus. Biophys J. 1989 Jun;55(6):1053–1080. doi: 10.1016/S0006-3495(89)82904-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dold F. G., Sanger J. M., Sanger J. W. Intact alpha-actinin molecules are needed for both the assembly of actin into the tails and the locomotion of Listeria monocytogenes inside infected cells. Cell Motil Cytoskeleton. 1994;28(2):97–107. doi: 10.1002/cm.970280202. [DOI] [PubMed] [Google Scholar]
  13. Evans E. New physical concepts for cell amoeboid motion. Biophys J. 1993 Apr;64(4):1306–1322. doi: 10.1016/S0006-3495(93)81497-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Forscher P., Lin C. H., Thompson C. Novel form of growth cone motility involving site-directed actin filament assembly. Nature. 1992 Jun 11;357(6378):515–518. doi: 10.1038/357515a0. [DOI] [PubMed] [Google Scholar]
  15. Fujimoto T. Calcium pump of the plasma membrane is localized in caveolae. J Cell Biol. 1993 Mar;120(5):1147–1157. doi: 10.1083/jcb.120.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fushimi K., Verkman A. S. Low viscosity in the aqueous domain of cell cytoplasm measured by picosecond polarization microfluorimetry. J Cell Biol. 1991 Feb;112(4):719–725. doi: 10.1083/jcb.112.4.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goldberg M. B., Theriot J. A. Shigella flexneri surface protein IcsA is sufficient to direct actin-based motility. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6572–6576. doi: 10.1073/pnas.92.14.6572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hartwig J. H. Mechanisms of actin rearrangements mediating platelet activation. J Cell Biol. 1992 Sep;118(6):1421–1442. doi: 10.1083/jcb.118.6.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hill T. L., Kirschner M. W. Bioenergetics and kinetics of microtubule and actin filament assembly-disassembly. Int Rev Cytol. 1982;78:1–125. [PubMed] [Google Scholar]
  20. Hooper N. M. More than just a membrane anchor. Curr Biol. 1992 Nov;2(11):617–619. doi: 10.1016/0960-9822(92)90183-b. [DOI] [PubMed] [Google Scholar]
  21. Isambert H., Venier P., Maggs A. C., Fattoum A., Kassab R., Pantaloni D., Carlier M. F. Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin, and muscle regulatory proteins. J Biol Chem. 1995 May 12;270(19):11437–11444. doi: 10.1074/jbc.270.19.11437. [DOI] [PubMed] [Google Scholar]
  22. Janmey P. A., Hvidt S., Käs J., Lerche D., Maggs A., Sackmann E., Schliwa M., Stossel T. P. The mechanical properties of actin gels. Elastic modulus and filament motions. J Biol Chem. 1994 Dec 23;269(51):32503–32513. [PubMed] [Google Scholar]
  23. Kocks C., Cossart P. Directional actin assembly by Listeria monocytogenes at the site of polar surface expression of the actA gene product involving the actin-bundling protein plastin (fimbrin). Infect Agents Dis. 1993 Aug;2(4):207–209. [PubMed] [Google Scholar]
  24. Kocks C., Hellio R., Gounon P., Ohayon H., Cossart P. Polarized distribution of Listeria monocytogenes surface protein ActA at the site of directional actin assembly. J Cell Sci. 1993 Jul;105(Pt 3):699–710. doi: 10.1242/jcs.105.3.699. [DOI] [PubMed] [Google Scholar]
  25. Kreis T. E. Regulation of vesicular and tubular membrane traffic of the Golgi complex by coat proteins. Curr Opin Cell Biol. 1992 Aug;4(4):609–615. doi: 10.1016/0955-0674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  26. Käs J., Strey H., Tang J. X., Finger D., Ezzell R., Sackmann E., Janmey P. A. F-actin, a model polymer for semiflexible chains in dilute, semidilute, and liquid crystalline solutions. Biophys J. 1996 Feb;70(2):609–625. doi: 10.1016/S0006-3495(96)79630-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lee J., Leonard M., Oliver T., Ishihara A., Jacobson K. Traction forces generated by locomoting keratocytes. J Cell Biol. 1994 Dec;127(6 Pt 2):1957–1964. doi: 10.1083/jcb.127.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lin C. H., Forscher P. Growth cone advance is inversely proportional to retrograde F-actin flow. Neuron. 1995 Apr;14(4):763–771. doi: 10.1016/0896-6273(95)90220-1. [DOI] [PubMed] [Google Scholar]
  29. Marchand J. B., Moreau P., Paoletti A., Cossart P., Carlier M. F., Pantaloni D. Actin-based movement of Listeria monocytogenes: actin assembly results from the local maintenance of uncapped filament barbed ends at the bacterium surface. J Cell Biol. 1995 Jul;130(2):331–343. doi: 10.1083/jcb.130.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mortara R. A., Koch G. L. An association between actin and nucleocapsid polypeptides in isolated murine retroviral particles. J Submicrosc Cytol Pathol. 1989 Apr;21(2):295–306. [PubMed] [Google Scholar]
  31. Nanavati D., Ashton F. T., Sanger J. M., Sanger J. W. Dynamics of actin and alpha-actinin in the tails of Listeria monocytogenes in infected PtK2 cells. Cell Motil Cytoskeleton. 1994;28(4):346–358. doi: 10.1002/cm.970280408. [DOI] [PubMed] [Google Scholar]
  32. Oliver T., Dembo M., Jacobson K. Traction forces in locomoting cells. Cell Motil Cytoskeleton. 1995;31(3):225–240. doi: 10.1002/cm.970310306. [DOI] [PubMed] [Google Scholar]
  33. Oliver T., Lee J., Jacobson K. Forces exerted by locomoting cells. Semin Cell Biol. 1994 Jun;5(3):139–147. doi: 10.1006/scel.1994.1018. [DOI] [PubMed] [Google Scholar]
  34. Peskin C. S., Odell G. M., Oster G. F. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys J. 1993 Jul;65(1):316–324. doi: 10.1016/S0006-3495(93)81035-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pollard T. D. Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments. J Cell Biol. 1986 Dec;103(6 Pt 2):2747–2754. doi: 10.1083/jcb.103.6.2747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ridley A. J. Membrane ruffling and signal transduction. Bioessays. 1994 May;16(5):321–327. doi: 10.1002/bies.950160506. [DOI] [PubMed] [Google Scholar]
  37. Roberts T. M., Stewart M. Nematode sperm locomotion. Curr Opin Cell Biol. 1995 Feb;7(1):13–17. doi: 10.1016/0955-0674(95)80039-5. [DOI] [PubMed] [Google Scholar]
  38. Sanger J. M., Mittal B., Southwick F. S., Sanger J. W. Listeria monocytogenes intracellular migration: inhibition by profilin, vitamin D-binding protein and DNase I. Cell Motil Cytoskeleton. 1995;30(1):38–49. doi: 10.1002/cm.970300106. [DOI] [PubMed] [Google Scholar]
  39. Sanger J. M., Sanger J. W., Southwick F. S. Host cell actin assembly is necessary and likely to provide the propulsive force for intracellular movement of Listeria monocytogenes. Infect Immun. 1992 Sep;60(9):3609–3619. doi: 10.1128/iai.60.9.3609-3619.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shariff A., Luna E. J. Diacylglycerol-stimulated formation of actin nucleation sites at plasma membranes. Science. 1992 Apr 10;256(5054):245–247. doi: 10.1126/science.1373523. [DOI] [PubMed] [Google Scholar]
  41. Sheetz M. P. Cell migration by graded attachment to substrates and contraction. Semin Cell Biol. 1994 Jun;5(3):149–155. doi: 10.1006/scel.1994.1019. [DOI] [PubMed] [Google Scholar]
  42. Small J. V., Herzog M., Anderson K. Actin filament organization in the fish keratocyte lamellipodium. J Cell Biol. 1995 Jun;129(5):1275–1286. doi: 10.1083/jcb.129.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Small J. V., Isenberg G., Celis J. E. Polarity of actin at the leading edge of cultured cells. Nature. 1978 Apr 13;272(5654):638–639. doi: 10.1038/272638a0. [DOI] [PubMed] [Google Scholar]
  44. Small J. V. Lamellipodia architecture: actin filament turnover and the lateral flow of actin filaments during motility. Semin Cell Biol. 1994 Jun;5(3):157–163. doi: 10.1006/scel.1994.1020. [DOI] [PubMed] [Google Scholar]
  45. Smith G. A., Portnoy D. A., Theriot J. A. Asymmetric distribution of the Listeria monocytogenes ActA protein is required and sufficient to direct actin-based motility. Mol Microbiol. 1995 Sep;17(5):945–951. doi: 10.1111/j.1365-2958.1995.mmi_17050945.x. [DOI] [PubMed] [Google Scholar]
  46. Southwick F. S., Purich D. L. Arrest of Listeria movement in host cells by a bacterial ActA analogue: implications for actin-based motility. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5168–5172. doi: 10.1073/pnas.91.11.5168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Southwick F. S., Purich D. L. Inhibition of Listeria locomotion by mosquito oostatic factor, a natural oligoproline peptide uncoupler of profilin action. Infect Immun. 1995 Jan;63(1):182–190. doi: 10.1128/iai.63.1.182-190.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Southwick F. S., Purich D. L. Intracellular pathogenesis of listeriosis. N Engl J Med. 1996 Mar 21;334(12):770–776. doi: 10.1056/NEJM199603213341206. [DOI] [PubMed] [Google Scholar]
  49. Stossel T. P. On the crawling of animal cells. Science. 1993 May 21;260(5111):1086–1094. doi: 10.1126/science.8493552. [DOI] [PubMed] [Google Scholar]
  50. Stossel T. P. The machinery of cell crawling. Sci Am. 1994 Sep;271(3):54-5, 58-63. doi: 10.1038/scientificamerican0994-54. [DOI] [PubMed] [Google Scholar]
  51. Swanson J. A., Baer S. C. Phagocytosis by zippers and triggers. Trends Cell Biol. 1995 Mar;5(3):89–93. doi: 10.1016/s0962-8924(00)88956-4. [DOI] [PubMed] [Google Scholar]
  52. Theriot J. A. Actin filament dynamics in cell motility. Adv Exp Med Biol. 1994;358:133–145. doi: 10.1007/978-1-4615-2578-3_13. [DOI] [PubMed] [Google Scholar]
  53. Theriot J. A., Mitchison T. J. Actin microfilament dynamics in locomoting cells. Nature. 1991 Jul 11;352(6331):126–131. doi: 10.1038/352126a0. [DOI] [PubMed] [Google Scholar]
  54. Theriot J. A., Mitchison T. J., Tilney L. G., Portnoy D. A. The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. Nature. 1992 May 21;357(6375):257–260. doi: 10.1038/357257a0. [DOI] [PubMed] [Google Scholar]
  55. Theriot J. A. The cell biology of infection by intracellular bacterial pathogens. Annu Rev Cell Dev Biol. 1995;11:213–239. doi: 10.1146/annurev.cb.11.110195.001241. [DOI] [PubMed] [Google Scholar]
  56. Tilney L. G., DeRosier D. J., Tilney M. S. How Listeria exploits host cell actin to form its own cytoskeleton. I. Formation of a tail and how that tail might be involved in movement. J Cell Biol. 1992 Jul;118(1):71–81. doi: 10.1083/jcb.118.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Tilney L. G., DeRosier D. J., Weber A., Tilney M. S. How Listeria exploits host cell actin to form its own cytoskeleton. II. Nucleation, actin filament polarity, filament assembly, and evidence for a pointed end capper. J Cell Biol. 1992 Jul;118(1):83–93. doi: 10.1083/jcb.118.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Tilney L. G., Portnoy D. A. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite, Listeria monocytogenes. J Cell Biol. 1989 Oct;109(4 Pt 1):1597–1608. doi: 10.1083/jcb.109.4.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Toyoshima C., Sasabe H., Stokes D. L. Three-dimensional cryo-electron microscopy of the calcium ion pump in the sarcoplasmic reticulum membrane. Nature. 1993 Apr 1;362(6419):467–471. doi: 10.1038/362469a0. [DOI] [PubMed] [Google Scholar]
  60. Valberg P. A., Feldman H. A. Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys J. 1987 Oct;52(4):551–561. doi: 10.1016/S0006-3495(87)83244-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Winokur R., Hartwig J. H. Mechanism of shape change in chilled human platelets. Blood. 1995 Apr 1;85(7):1796–1804. [PubMed] [Google Scholar]
  62. Zhu C., Skalak R. A continuum model of protrusion of pseudopod in leukocytes. Biophys J. 1988 Dec;54(6):1115–1137. doi: 10.1016/S0006-3495(88)83047-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Zhukarev V., Ashton F., Sanger J. M., Sanger J. W., Shuman H. Organization and structure of actin filament bundles in Listeria-infected cells. Cell Motil Cytoskeleton. 1995;30(3):229–246. doi: 10.1002/cm.970300307. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES