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.

  • Brief Communication
  • Published:

Membrane microviscosity regulates endothelial cell motility

Nature Cell Biology volume 4, pages 894–900 (2002)Cite this article

Abstract

Endothelial cell (EC) movement is an initiating and rate-limiting event in the neogenesis and repair of blood vessels. Here, we explore the hypothesis that microviscosity of the plasma membrane (PM) is a key physiological regulator of cell movement. Aortic ECs treated with membrane-active agents, such as α-tocopherol, cholesterol and lysophospholipids, exhibited a biphasic dependency on membrane microviscosity, in which moderate increases enhanced EC migration, but increases beyond a threshold markedly inhibited migration. Surprisingly, angiogenic growth factors, that is, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), also increased membrane microviscosity, as measured in live cells by fluorescence recovery after photobleaching (FRAP). The localization of Rac to the PM was modified in cells treated with membrane-active agents or growth factors, suggesting a molecular mechanism for how membrane microviscosity influences cell movement. Our data show that angiogenic growth factors, as well as certain lipophilic molecules, regulate cell motility through alterations in membrane properties and the consequent relocalization of critical signalling molecules to membranes.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: α-Tocopherol abrogates the antimigratory activity of lysoPC.
Figure 2: Effect of membrane-active agents on EC migration and membrane microviscosity.
Figure 3: Biphasic influence of membrane microviscosity on EC migration.
Figure 4: bFGF and VEGF165 increase EC membrane microviscosity.
Figure 5: Influence of membrane microviscosity on the localization of Rac.

Similar content being viewed by others

References

  1. Horwitz, A. R. & Parsons, J. T. Science 286, 1102–1103 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Lauffenburger, D. A. & Horwitz, A. F. Cell 84, 359–369 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Zetter, B. R. Annu. Rev. Med. 49, 407–424 (1998).

    Article  CAS  PubMed  Google Scholar 

  4. Murugesan, G., Chisolm, G. M. & Fox, P. L. J. Cell Biol. 120, 1011–1019 (1993).

    Article  CAS  PubMed  Google Scholar 

  5. Murugesan, G. & Fox, P. L. J. Clin. Invest. 97, 2736–2744 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sheetz, M. P., Painter, R. G. & Singer, S. J. J. Cell Biol. 70, 193–203 (1976).

    Article  CAS  PubMed  Google Scholar 

  7. Kugiyama, K. et al. Atherosclerosis 143, 201–204 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Urano, S. et al. J. Biol. Chem. 267, 18365–18370 (1992).

    CAS  PubMed  Google Scholar 

  9. Pryor, W. A. Free Radic. Biol. Med. 28, 141–164 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Yeagle, P. L., Albert, A. D., Boesze-Battaglia, K., Young, J. & Frye, J. Biophys. J. 57, 413–424 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stillwell, W., Dallman, T., Dumaual, A. C., Crump, F. T. & Jenski, L. J. Biochemistry 35, 13353–13362 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Chang, H. M., Reitstetter, R. & Gruener, R. J. Membr. Biol. 145, 13–19 (1995).

    Article  CAS  PubMed  Google Scholar 

  13. Lundbæk, J. A. & Andersen, O. S. J. Gen. Physiol. 104, 645–673 (1994).

    Article  PubMed  Google Scholar 

  14. Van Corven, E. J., Groenink, A., Jalink, K., Eichholtz, T. & Moolenaar, W. H. Cell 59, 45–54 (1989).

    Article  CAS  PubMed  Google Scholar 

  15. Axelrod, D., Koppel, D. E., Schlessinger, J., Elson, E. & Webb, W. W. Biophys. J. 16, 1055–1069 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nobes, C. D. & Hall, A. Cell 81, 53–62 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Bretscher, M. S. Cell 85, 465–467 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Felder, S. & Elson, E. L. J. Cell Biol. 111, 2513–2526 (1990).

    Article  CAS  PubMed  Google Scholar 

  19. Raucher, D. & Sheetz, M. P. J. Cell Biol. 148, 127–136 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Marom, M., Ben-Baruch, G., Roitelman, J. & Kloog, Y. Cell Mol. Neurobiol. 14, 119–132 (1994).

    Article  CAS  PubMed  Google Scholar 

  21. Scheiffele, P., Rietveld, A., Wilk, T. & Simons, K. J. Biol. Chem. 274, 2038–2044 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Pralle, A., Keller, P., Florin, E. L., Simons, K. & Hörber, J. K. J. Cell Biol. 148, 997–1008 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gómez-Moutón, C. et al. Proc. Natl Acad. Sci USA 98, 9642–9647 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Isshiki, M. et al. J. Cell Sci. 115, 475–484 (2002).

    CAS  PubMed  Google Scholar 

  25. Del Pozo, M. A., Price, L. S., Alderson, N. B., Ren, X. D. & Schwartz, M. A. EMBO J. 19, 2008–2014 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chatterjee, S., Cheung, H. C. & Hunter, E. Proc. Natl Acad. Sci. USA 79, 835–839 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shklar, G. & Schwartz, J. L. Eur. J. Cancer 32B, 114–119 (1996).

    Article  CAS  Google Scholar 

  28. Butkerait, P. et al. J. Biol. Chem. 270, 18691–18699 (1995).

    Article  CAS  PubMed  Google Scholar 

  29. Sommer, A. et al. J. Biol. Chem. 267, 24217–24222 (1992).

    CAS  PubMed  Google Scholar 

  30. Smart, E. J., Ying, Y. S., Mineo, C. & Anderson, R. G. Proc. Natl Acad. Sci. USA 92, 10104–10108 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank B. Anand-Apte for helpful discussions. This work was supported by National Institutes of Health grants HL/CA54519 and HL29582 to P.L.F. and HL64357 to L.M.G., National Aeronautics and Space Administration grant 96-HEDS-04 to P.L.F. and a Fellowship from the American Heart Association, Ohio Valley Affiliate to P.K.G.

Author information

Authors and Affiliations

  1. Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, 44195, OH, USA

    Prabar K. Ghosh, Amit Vasanji & Paul L. Fox

  2. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, 44106, OH, USA

    Amit Vasanji & Steven J. Eppell

  3. Department of Clinical Pathology, Cleveland Clinic Foundation, Cleveland, 44195, OH, USA

    Gurunathan Murugesan

  4. Departments of Biomedical Engineering and Vascular Surgery, Cleveland Clinic Foundation, Cleveland, 44195, OH, USA

    Linda M. Graham

Authors
  1. Prabar K. Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amit Vasanji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gurunathan Murugesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven J. Eppell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Linda M. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul L. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul L. Fox.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ghosh, P., Vasanji, A., Murugesan, G. et al. Membrane microviscosity regulates endothelial cell motility. Nat Cell Biol 4, 894–900 (2002). https://doi.org/10.1038/ncb873

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb873

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