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.

  • Opinion
  • Published:

Blebs lead the way: how to migrate without lamellipodia

Abstract

Blebs are spherical membrane protrusions that are produced by contractions of the actomyosin cortex. Blebs are often considered to be a hallmark of apoptosis; however, blebs are also frequently observed during cytokinesis and during migration in three-dimensional cultures and in vivo. For tumour cells and a number of embryonic cells, blebbing migration seems to be a common alternative to the more extensively studied lamellipodium-based motility. We argue that blebs should be promoted to a more prominent place in the world of cellular protrusions.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: The bleb life cycle.
Figure 2: Examples of cell blebbing.
Figure 3: Generating polarized blebbing.
Figure 4: From blebbing to movement.

Similar content being viewed by others

References

  1. Alberts, B. et al. Molecular Biology of the Cell (Garland, New York, 2008).

    Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Robertson, A. M., Bird, C. C., Waddell, A. W. & Currie, A. R. Morphological aspects of glucocorticoid-induced cell death in human lymphoblastoid cells. J. Pathol. 126, 181–187 (1978).

    Article  CAS  Google Scholar 

  4. Trinkaus, J. P. Surface activity and locomotion of Fundulus deep cells during blastula and gastrula stages. Dev. Biol. 30, 69–103 (1973).

    Article  CAS  Google Scholar 

  5. Blaser, H. et al. Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. Dev. Cell 11, 613–627 (2006).

    Article  CAS  Google Scholar 

  6. Sahai, E. & Marshall, C. J. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nature Cell Biol. 5, 711–719 (2003).

    CAS  PubMed  Google Scholar 

  7. Yoshida, K. & Soldati, T. Dissection of amoeboid movement into two mechanically distinct modes. J. Cell Sci. 119, 3833–3844 (2006).

    Article  CAS  Google Scholar 

  8. Fackler, O. T. & Grosse, R. Cell motility through plasma membrane blebbing. J. Cell Biol. 181, 879–884 (2008).

    Article  CAS  Google Scholar 

  9. Friedl, P. & Wolf, K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nature Rev. Cancer 3, 362–374 (2003).

    Article  CAS  Google Scholar 

  10. Pinner, S. & Sahai, E. PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nature Cell Biol. 10, 127–137 (2008).

    Article  CAS  Google Scholar 

  11. Holtfreter, J. Properties and functions of the surface coat in amphibian embryos. J. Exp. Zool. 93, 251–323 (1943).

    Article  Google Scholar 

  12. Wourms, J. P. The developmental biology of annual fishes. II. Naturally occurring dispersion and reaggregation of blastomers during the development of annual fish eggs. J. Exp. Zool. 182, 169–200 (1972).

    Article  CAS  Google Scholar 

  13. Kageyama, T. Motility and locomotion of embryonic cells of the medaka, Oryzias latipes, during early development. Dev. Growth Differ. 19, 103–110 (1977).

    Article  Google Scholar 

  14. Concha, M. L. & Adams, R. J. Oriented cell divisions and cellular morphogenesis in the zebrafish gastrula and neurula: a time-lapse analysis. Development 125, 983–994 (1998).

    CAS  PubMed  Google Scholar 

  15. Fink, R. D. & Trinkaus, J. P. Fundulus deep cells: directional migration in response to epithelial wounding. Dev. Biol. 129, 179–190 (1988).

    Article  CAS  Google Scholar 

  16. Trinkaus, J. P. Ingression during early gastrulation of Fundulus. Dev. Biol. 177, 356–370 (1996).

    Article  CAS  Google Scholar 

  17. Kubota, H. Y. Creeping locomotion of the endodermal cells dissociated from gastrulae of the Japanese newt, Cynops pyrrhogaster. Exp. Cell Res. 133, 137–148 (1981).

    Article  CAS  Google Scholar 

  18. Satoh, N., Kageyama, T. & Sirakami, K. T. Motility of dissociated embryonic cells in Xenopus laevis: its significance to morphogenetic movements. Dev. Growth Diff. 18, 55–67 (1976).

    Article  Google Scholar 

  19. Jaglarz, M. K. & Howard, K. R. The active migration of Drosophila primordial germ cells. Development 121, 3495–3503 (1995).

    CAS  PubMed  Google Scholar 

  20. Mast, S. O. Structure, movement, locomotion, and stimulation of amoeba. J. Morphol. Physiol. 41, 347–425 (1926).

    Article  Google Scholar 

  21. Yanai, M., Kenyon, C. M., Butler, J. P., Macklem, P. T. & Kelly, S. M. Intracellular pressure is a motive force for cell motion in Amoeba proteus. Cell. Motil. Cytoskeleton 33, 22–29 (1996).

    Article  CAS  Google Scholar 

  22. Stockem, W., Hoffmann, H. U. & Gawlitta, W. Spatial organization and fine structure of the cortical filament layer in normal locomoting Amoeba proteus. Cell Tissue Res. 221, 505–519 (1982).

    Article  CAS  Google Scholar 

  23. Pomorski, P. et al. Actin dynamics in Amoeba proteus motility. Protoplasma 231, 31–41 (2007).

    Article  CAS  Google Scholar 

  24. Langridge, P. D. & Kay, R. R. Blebbing of Dictyostelium cells in response to chemoattractant. Exp. Cell Res. 312, 2009–2017 (2006).

    Article  CAS  Google Scholar 

  25. Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267–277 (2003).

    Article  CAS  Google Scholar 

  26. Voura, E. B., Sandig, M. & Siu, C. H. Cell–cell interactions during transendothelial migration of tumor cells. Microsc. Res. Tech. 43, 265–275 (1998).

    Article  CAS  Google Scholar 

  27. Haston, W. S. & Shields, J. M. Contraction waves in lymphocyte locomotion. J. Cell Sci. 68, 227–241 (1984).

    CAS  PubMed  Google Scholar 

  28. Keller, H. & Eggli, P. Protrusive activity, cytoplasmic compartmentalization, and restriction rings in locomoting blebbing Walker carcinosarcoma cells are related to detachment of cortical actin from the plasma membrane. Cell. Motil. Cytoskeleton 41, 181–193 (1998).

    Article  CAS  Google Scholar 

  29. Keller, H., Rentsch, P. & Hagmann, J. Differences in cortical actin structure and dynamics document that different types of blebs are formed by distinct mechanisms. Exp. Cell Res. 277, 161–172 (2002).

    Article  CAS  Google Scholar 

  30. Sroka, J., von Gunten, M., Dunn, G. A. & Keller, H. U. Phenotype modulation in non-adherent and adherent sublines of Walker carcinosarcoma cells: the role of cell-substratum contacts and microtubules in controlling cell shape, locomotion and cytoskeletal structure. Int. J. Biochem. Cell Biol. 34, 882–899 (2002).

    Article  CAS  Google Scholar 

  31. Fink, R. D. In vivo cytoskeletal dynamics of living fish embryos. Movie #2: deep cell circus movements: actin dynamics. Mount Holyoke College [online], (2003).

  32. Charras, G. T. A short history of blebbing. J. Microsc. (in the press).

  33. Cunningham, C. C. Actin polymerization and intracellular solvent flow in cell surface blebbing. J. Cell Biol. 129, 1589–1599 (1995).

    Article  CAS  Google Scholar 

  34. Paluch, E., Piel, M., Prost, J., Bornens, M. & Sykes, C. Cortical actomyosin breakage triggers shape oscillations in cells and cell fragments. Biophys. J. 89, 724–733 (2005).

    Article  CAS  Google Scholar 

  35. Paluch, E., van der Gucht, J. & Sykes, C. Cracking up: symmetry breaking in cellular systems. J. Cell Biol. 175, 687–692 (2006).

    Article  CAS  Google Scholar 

  36. Coleman, M. L. et al. Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nature Cell Biol. 3, 339–345 (2001).

    Article  CAS  Google Scholar 

  37. Mills, J. C., Stone, N. L. & Pittman, R. N. Extranuclear apoptosis. The role of the cytoplasm in the execution phase. J. Cell Biol. 146, 703–708 (1999).

    Article  CAS  Google Scholar 

  38. Tournaviti, S. et al. SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility. J. Cell Sci. 120, 3820–3829 (2007).

    Article  CAS  Google Scholar 

  39. Gutjahr, M. C., Rossy, J. & Niggli, V. Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells. Exp. Cell Res. 308, 422–438 (2005).

    Article  CAS  Google Scholar 

  40. Fujinami, N. Studies on the mechanism of circus movement in dissociated embryonic cells of a teleost, Oryzias latipes: fine-structural observations. J. Cell Sci. 22, 133–147 (1976).

    CAS  PubMed  Google Scholar 

  41. Tickle, C. & Trinkaus, J. P. Some clues as to the formation of protrusions by Fundulus deep cells. J. Cell Sci. 26, 139–150 (1977).

    CAS  PubMed  Google Scholar 

  42. Fedier, A., Eggli, P. & Keller, H. U. Redistribution of surface-bound con A is quantitatively related to the movement of cells developing polarity. Cell. Motil. Cytoskeleton 44, 44–57 (1999).

    Article  CAS  Google Scholar 

  43. Charras, G. T., Hu, C. K., Coughlin, M. & Mitchison, T. J. Reassembly of contractile actin cortex in cell blebs. J. Cell Biol. 175, 477–490 (2006).

    Article  CAS  Google Scholar 

  44. Cunningham, C. C. et al. Actin-binding protein requirement for cortical stability and efficient locomotion. Science 255, 325–327 (1992).

    Article  CAS  Google Scholar 

  45. Decave, E. et al. Shear flow-induced motility of Dictyostelium discoideum cells on solid substrate. J. Cell Sci. 116, 4331–4343 (2003).

    Article  CAS  Google Scholar 

  46. Rossy, J., Gutjahr, M. C., Blaser, N., Schlicht, D. & Niggli, V. Ezrin/moesin in motile Walker 256 carcinosarcoma cells: signal-dependent relocalization and role in migration. Exp. Cell Res. 313, 1106–1120 (2007).

    Article  CAS  Google Scholar 

  47. Paluch, E., Sykes, C., Prost, J. & Bornens, M. Dynamic modes of the cortical actomyosin gel during cell locomotion and division. Trends Cell Biol. 16, 5–10 (2006).

    Article  CAS  Google Scholar 

  48. Charras, G. T., Yarrow, J. C., Horton, M. A., Mahadevan, L. & Mitchison, T. J. Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435, 365–369 (2005).

    Article  CAS  Google Scholar 

  49. Mitchison, T. J., Charras, G. T. & Mahadevan, L. Implications of a poroelastic cytoplasm for the dynamics of animal cell shape. Semin. Cell Dev. Biol. 19, 215–223 (2008).

    Article  CAS  Google Scholar 

  50. Grebecki, A., Grebecka, L. & Wasik, A. Minipodia and rosette contacts are adhesive organelles present in free-living amoebae. Cell Biol. Int. 25, 1279–1283 (2001).

    Article  CAS  Google Scholar 

  51. Trinkaus, J. P. & Lentz, T. L. Surface specializations of Fundulus cells and their relation to cell movements during gastrulation. J. Cell Biol. 32, 139–153 (1967).

    Article  CAS  Google Scholar 

  52. Blaser, H. et al. Transition from non-motile behaviour to directed migration during early PGC development in zebrafish. J. Cell Sci. 118, 4027–4038 (2005).

    Article  CAS  Google Scholar 

  53. Malawista, S. E., de Boisfleury Chevance, A. & Boxer, L. A. Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from a patient with leukocyte adhesion deficiency-1: normal displacement in close quarters via chimneying. Cell. Motil. Cytoskeleton 46, 183–189 (2000).

    Article  CAS  Google Scholar 

  54. Svitkina, T. M., Verkhovsky, A. B., McQuade, K. M. & Borisy, G. G. Analysis of the actin-myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 139, 397–415 (1997).

    Article  CAS  Google Scholar 

  55. Bereiter-Hahn, J., Luck, M., Miebach, T., Stelzer, H. K. & Voth, M. Spreading of trypsinized cells: cytoskeletal dynamics and energy requirements. J. Cell Sci. 96, 171–188 (1990).

    PubMed  Google Scholar 

  56. Balaban, N. Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nature Cell Biol. 3, 466–472 (2001).

    Article  CAS  Google Scholar 

  57. Giannone, G. et al. Lamellipodial actin mechanically links myosin activity with adhesion-site formation. Cell 128, 561–575 (2007).

    Article  CAS  Google Scholar 

  58. Lo, C. M., Wang, H. B., Dembo, M. & Wang, Y. L. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79, 144–152 (2000).

    Article  CAS  Google Scholar 

  59. Mills, J. C., Stone, N. L., Erhardt, J. & Pittman, R. N. Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J. Cell Biol. 140, 627–636 (1998).

    Article  CAS  Google Scholar 

  60. Sebbagh, M. et al. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nature Cell Biol. 3, 346–352 (2001).

    Article  CAS  Google Scholar 

  61. Sebbagh, M., Hamelin, J., Bertoglio, J., Solary, E. & Breard, J. Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner. J. Exp. Med. 201, 465–471 (2005).

    Article  CAS  Google Scholar 

  62. Segundo, C. et al. Surface molecule loss and bleb formation by human germinal center B cells undergoing apoptosis: role of apoptotic blebs in monocyte chemotaxis. Blood 94, 1012–1020 (1999).

    CAS  Google Scholar 

  63. Barros, L. F. et al. Apoptotic and necrotic blebs in epithelial cells display similar neck diameters but different kinase dependency. Cell Death Differ. 10, 687–697 (2003).

    Article  CAS  Google Scholar 

  64. Fishkind, D. J., Cao, L. G. & Wang, Y. L. Microinjection of the catalytic fragment of myosin light chain kinase into dividing cells: effects on mitosis and cytokinesis. J. Cell Biol. 114, 967–975 (1991).

    Article  CAS  Google Scholar 

  65. Hickson, G. R., Echard, A. & O'Farrell, P. H. Rho-kinase controls cell shape changes during cytokinesis. Curr. Biol. 16, 359–370 (2006).

    Article  CAS  Google Scholar 

  66. Tokumitsu, T. & Maramorosch, K. Cytoplasmic protrusions in insect cells during mitosis in vitro. J. Cell Biol. 34, 677–683 (1967).

    Article  CAS  Google Scholar 

  67. Strangeways, T. Observations on the changes seen in living cells during growth and division. Proc. R. Soc. Lond., B, Biol. Sci. 94, 137–141 (1922).

    Article  Google Scholar 

  68. Erickson, C. A. & Trinkaus, J. P. Microvilli and blebs as sources of reserve surface membrane during cell spreading. Exp. Cell Res. 99, 375–384 (1976).

    Article  CAS  Google Scholar 

  69. Mercer, J. & Helenius, A. Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells. Science 320, 531–535 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

G.C. is a Royal Society University Research Fellow. E.P. is supported by the Polish Ministry of Science and Higher Education from science funds for the years 2006–2009, and by the Max Planck Society. The authors wish to thank M. Biro and A.G. Clark for careful reading of the manuscript and helpful suggestions.

Author information

Authors and Affiliations

Authors

Related links

Related links

FURTHER INFORMATION

Guillaume Charras' homepage

Ewa Paluch's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Charras, G., Paluch, E. Blebs lead the way: how to migrate without lamellipodia. Nat Rev Mol Cell Biol 9, 730–736 (2008). https://doi.org/10.1038/nrm2453

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2453

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