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:

Glycans pattern the phase behaviour of lipid membranes

Abstract

Hydrated networks of glycans (polysaccharides)—in the form of cell walls, periplasms or gel-like matrices—are ubiquitously present adjacent to cellular plasma membranes1,2,3,4. Yet, despite their abundance, the function of glycans in the extracellular milieu is largely unknown5. Here we show that the spatial configuration of glycans controls the phase behaviour of multiphase model lipid membranes: inhomogeneous glycan networks stabilize large lipid domains at the characteristic length scale of the network, whereas homogeneous networks suppress macroscopic lipid phase separation. We also find that glycan-patterned phase separation is thermally reversible—thus indicating that the effect is thermodynamic rather than kinetic—and that phase patterning probably results from a preferential interaction of glycans with ordered lipid phases. These findings have implications for membrane-mediated transport processes6,7,8, potentially rationalize long-standing observations that differentiate the behaviour of native and model membranes9,10,11,12,13 and may indicate an intimate coupling between cellular lipidomes and glycomes.

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

Access options

Buy this article

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

Figure 1: Preparation of hydrated glycan networks with varying spatial configurations.
Figure 2: Inhomogeneous glycan networks pattern the formation of macroscopic time-stable lipid domains in multiphase membranes.
Figure 3: Lipid domains on inhomogeneous glycan networks are in thermal equilibrium as evidenced by reversible temperature-induced phase transitions.
Figure 4: Homogeneous glycan networks suppress macroscopic phase separation in multiphase lipid membranes.
Figure 5: Gross topography and microstructural roughness of the inhomogeneous glycan networks are not the dominant mechanism for the patterning of phase separation of lipid membranes.

Similar content being viewed by others

References

  1. Alberts, B. et al. Molecular Biology of the Cell 4th edn (Garland Science, 2002).

    Google Scholar 

  2. Laurent, T. & Fraser, J. Hyaluronan. The FASEB J. 6, 2397–2404 (1992).

    Article  CAS  Google Scholar 

  3. Masako, O. The ultrastructure of yeast: Cell wall structure and formation. Micron 29, 207–233 (1998).

    Article  Google Scholar 

  4. Somerville, C. et al. Toward a systems approach to understanding plant-cell walls. Science 306, 2206–2211 (2004).

    Article  CAS  Google Scholar 

  5. Marth, J. D. A unified vision of the building blocks of life. Nature Cell Biol. 10, 1015–1016 (2008).

    Article  CAS  Google Scholar 

  6. Lingwood, D. & Simons, K. Lipid rafts as a membrane-organizing principle. Science 327, 46–50 (2010).

    Article  CAS  Google Scholar 

  7. Brown, D. A. & London, E. Functions of lipid rafts in biological membranes. Annu. Rev. Cell Dev. Biol. 14, 111–136 (1998).

    Article  CAS  Google Scholar 

  8. Engelman, D. M. Membranes are more mosaic than fluid. Nature 438, 578–580 (2005).

    Article  CAS  Google Scholar 

  9. Munro, S. Lipid rafts: Elusive or illusive? Cell 115, 377–388 (2003).

    Article  CAS  Google Scholar 

  10. Yethiraj, A. & Weisshaar, J. C. Why are lipid rafts not observed in vivo? Biophys. J. 93, 3113–3119 (2007).

    Article  CAS  Google Scholar 

  11. Veatch, S. L. & Keller, S. L. Organization in lipid membranes containing cholesterol. Phys. Rev. Lett. 89, 268101 (2002).

    Article  Google Scholar 

  12. Baumgart, T., Hess, S. T. & Webb, W. W. Imaging coexisting fluid domains in biomembrane models coupling curvature and line tension. Nature 425, 821–824 (2003).

    Article  CAS  Google Scholar 

  13. McConnell, H. M. & Vrljic, M. Liquid–liquid immiscibility in membranes. Annu. Rev. Biophys. Biomol. Struct. 32, 469–492 (2003).

    Article  CAS  Google Scholar 

  14. Stottrup, B. L., Veatch, S. L. & Keller, S. L. Nonequilibrium behavior in supported lipid membranes containing cholesterol. Biophys. J. 86, 2942–2950 (2004).

    Article  CAS  Google Scholar 

  15. Parthasarathy, R., Yu, C. H. & Groves, J. T. Curvature-modulated phase separation in lipid bilayer membranes. Langmuir 22, 5095–5099 (2006).

    Article  CAS  Google Scholar 

  16. Groves, J. T., Ulman, N. & Boxer, S. G. Micropatterning fluid lipid bilayers on solid supports. Science 275, 651–653 (1997).

    Article  CAS  Google Scholar 

  17. Tanaka, M. & Sackmann, E. Polymer-supported membranes as models of the cell surface. Nature 437, 656–663 (2005).

    Article  CAS  Google Scholar 

  18. Smith, H. L. et al. Model lipid membranes on a tunable polymer cushion. Phys. Rev. Lett. 102, 228102 (2009).

    Article  Google Scholar 

  19. Wong, J. Y. et al. Polymer-cushioned bilayers. I. A structural study of various preparation methods using neutron reflectometry. Biophys. J. 77, 1445–1457 (1999).

    Article  CAS  Google Scholar 

  20. Sackmann, E. & Tanaka, M. Supported membranes on soft polymer cushions: Fabrication, characterization and applications. Trends Biotechnol. 18, 58–64 (2000).

    Article  CAS  Google Scholar 

  21. Watkins, E. B. et al. Structure and thermodynamics of lipid bilayers on polyethylene glycol cushions: Fact and fiction of PEG cushioned membranes. Langmuir 27, 13618–13628 (2011).

    Article  CAS  Google Scholar 

  22. Wagner, M. L. & Tamm, L. K. Tethered polymer-supported planar lipid bilayers for reconstitution of integral membrane proteins: Silane-polyethyleneglycol-lipid as a cushion and covalent linker. Biophys. J. 79, 1400–1414 (2000).

    Article  CAS  Google Scholar 

  23. Kraft, M. L., Weber, P. K., Longo, M. L., Hutcheon, I. D. & Boxer, S. G. Phase separation of lipid membranes analyzed with high-resolution secondary ion mass spectrometry. Science 313, 1948–1951 (2006).

    Article  CAS  Google Scholar 

  24. Yoon, T-Y. et al. Topographic control of lipid-raft reconstitution in model membranes. Nature Mater. 5, 281–285 (2006).

    Article  CAS  Google Scholar 

  25. Kahya, N., Scherfeld, D., Bacia, K., Poolman, B. & Schwille, P. Probing lipid mobility of raft-exhibiting model membranes by fluorescence correlation spectroscopy. J. Biol. Chem. 278, 28109–28115 (2003).

    Article  CAS  Google Scholar 

  26. Kaizuka, Y. & Groves, J. T. Structure and dynamics of supported intermembrane junctions. Biophys. J. 86, 905–912 (2004).

    Article  CAS  Google Scholar 

  27. Subramaniam, A. B., Lecuyer, S., Ramamurthi, K. S., Losick, R. & Stone, H. A. Particle/fluid interface replication as a means of producing topographically patterned polydimethylsiloxane surfaces for deposition of lipid bilayers. Adv. Mater. 22, 2142–2147 (2010).

    Article  CAS  Google Scholar 

  28. Dietrich, C. et al. Lipid rafts reconstituted in model membranes. Biophys. J. 80, 1417–1428 (2001).

    Article  CAS  Google Scholar 

  29. Pike, L. J. Rafts defined: A report on the Keystone symposium on lipid rafts and cell function. J. Lipid Res. 47, 1597–1598 (2006).

    Article  CAS  Google Scholar 

  30. Young, M. E. et al. The Sur7p family defines novel cortical domains in Saccharomyces cerevisiae, affects sphingolipid metabolism, and is involved in sporulation. Mol. Cell. Biol. 22, 927–934 (2002).

    Article  CAS  Google Scholar 

  31. Malinsky, J., Opekarová, M. & Tanner, W. The lateral compartmentation of the yeast plasma membrane. Yeast 27, 473–478 (2010).

    Article  CAS  Google Scholar 

  32. Smith, A. M., Vinchurkar, M., Gronbech-Jensen, N. & Parikh, A. N. Order at the edge of the bilayer: Membrane remodeling at the edge of a planar supported bilayer is accompanied by a localized phase change. J. Am. Chem. Soc. 132, 9320–9327 (2010).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Harvard MRSEC (DMR-0820484), Harvard Center for Brain Science Imaging Facility, the Harvard Center for Nanoscale Systems, and Princeton University for partial support of this research. We also thank S. Lecuyer and M. Staykova for comments on the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

A.B.S. made the initial observation of the effects of glycans on supported lipid membranes. H.A.S. and A.B.S. initiated research. A.B.S. designed and performed experiments and analysed data. A.B.S., G.G., V.N.M. and H.A.S. interpreted data and wrote the paper.

Corresponding authors

Correspondence to Anand Bala Subramaniam or Howard A. Stone.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 2252 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Subramaniam, A., Guidotti, G., Manoharan, V. et al. Glycans pattern the phase behaviour of lipid membranes. Nature Mater 12, 128–133 (2013). https://doi.org/10.1038/nmat3492

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat3492

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research