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Polyvalent choline phosphate as a universal biomembrane adhesive

Nature Materials volume 11, pages 468–476 (2012)Cite this article

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Abstract

Phospholipids in the cell membranes of all eukaryotic cells contain phosphatidyl choline (PC) as the headgroup. Here we show that hyperbranched polyglycerols (HPGs) decorated with the ’PC-inverse’ choline phosphate (CP) in a polyvalent fashion can electrostatically bind to a variety of cell membranes and to PC-containing liposomes, the binding strength depending on the number density of CP groups per macromolecule. We also show that HPG–CPs can cause cells to adhere with varying affinity to other cells, and that binding can be reversed by subsequent exposure to low molecular weight HPGs carrying small numbers of PCs. Moreover, PC-rich membranes adsorb and rapidly internalize fluorescent HPG–CP but not HPG–PC molecules, which suggests that HPG–CPs could be used as drug-delivery agents. CP-decorated polymers should find broad use, for instance as tissue sealants and in the self-assembly of lipid nanostructures.

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Figure 1: The universal biomembrane adhesive.
Figure 2: The biomembrane adhesion of polyvalent choline phosphate and its adhesion mechanism.
Figure 3: Effect of different parameters on the adsorption and reversibility of HPG–CP onto the RBC surface and association with morphology changes
Figure 4: Fluorescence-labelled HPG–CP adsorbed to PC-rich biomembranes.

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Acknowledgements

Financial support from Canadian Institutes of Health Research (CIHR), Canadian Blood Services (CBS), Canada Foundation for Innovation (CFI), and Michael Smith Foundation for Health Research (MSFHR) are gratefully acknowledged. The authors thank the Laboratory of Molecular Biophysics Macromolecular Hub at the University of British Columbia (UBC) Center for Blood Research for the use of their research facilities. These facilities are supported in part by grants from the Canada Foundation for Innovation and the Michael Smith Foundation for Health Research. J.N.K. acknowledges the New Investigator award from CIHR and CBS, as well as the Career Investigator Scholar award from MSFHR. The authors acknowledge Derrick Horne (UBC Bioimaging Facility) for technical assistance.

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Authors and Affiliations

  1. Centre for Blood Research, 2350 Health Sciences Mall, University of British Columbia, Vancouver V6T 1Z3, Canada

    Xifei Yu, Zonghua Liu, Johan Janzen, Irina Chafeeva, Sonja Horte, Wei Chen, Rajesh K. Kainthan, Jayachandran N. Kizhakkedathu & Donald E. Brooks

  2. Department of Pathology and Laboratory Medicine, Room G227 - 2211 Wesbrook Mall, University of British Columbia, Vancouver V6T 2B5, Canada

    Xifei Yu, Zonghua Liu, Johan Janzen, Irina Chafeeva, Sonja Horte, Rajesh K. Kainthan, Jayachandran N. Kizhakkedathu & Donald E. Brooks

  3. Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver V6T 1Z1, Canada

    Jayachandran N. Kizhakkedathu & Donald E. Brooks

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  1. Xifei Yu
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Contributions

X.Y., J.N.K. and D.E.B. conceived, designed and co-wrote the paper. X.Y., Z.L., I.C., S.H., W.C. and R.K.K performed the experiments. J.J. helped to analyse the data. All authors discussed the results and commented on the manuscript.

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Correspondence to Jayachandran N. Kizhakkedathu or Donald E. Brooks.

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Yu, X., Liu, Z., Janzen, J. et al. Polyvalent choline phosphate as a universal biomembrane adhesive. Nature Mater 11, 468–476 (2012). https://doi.org/10.1038/nmat3272

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