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Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization

Nature Chemistry volume 9, pages 537–545 (2017)Cite this article

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Abstract

The capability to graft synthetic polymers onto the surfaces of live cells offers the potential to manipulate and control their phenotype and underlying cellular processes. Conventional grafting-to strategies for conjugating preformed polymers to cell surfaces are limited by low polymer grafting efficiency. Here we report an alternative grafting-from strategy for directly engineering the surfaces of live yeast and mammalian cells through cell surface-initiated controlled radical polymerization. By developing cytocompatible PET-RAFT (photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization), synthetic polymers with narrow polydispersity (Mw/Mn < 1.3) could be obtained at room temperature in 5 minutes. This polymerization strategy enables chain growth to be initiated directly from chain-transfer agents anchored on the surface of live cells using either covalent attachment or non-covalent insertion, while maintaining high cell viability. Compared with conventional grafting-to approaches, these methods significantly improve the efficiency of grafting polymer chains and enable the active manipulation of cellular phenotypes.

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Figure 1: Strategies for engineering cell surfaces using synthetic polymers.
Figure 2: Characterizations of polymer coating and viability of the modified yeast cells.
Figure 3: Polymer cleavage and in situ chain extension confirmed well-defined covalent polymers with preserved chain end formed on the cell surface.
Figure 4: Utility of cell surface-initiated polymerization on yeast cells.
Figure 5: Cell surface-initiated polymerization on Jurkat cells.

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Acknowledgements

The authors thank the financial support of DARPA (N66001-14-2-4055), the Institute for Collaborative Biotechnologies through grants W911NF-09-0001 and W911QY-15-C-0026 from the US Army Research Office and the Garland Initiative. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. We acknowledge the support of UCSB Biological Nanostructures Laboratory and NRI-MCDB confocal microscopy facility (supported by NIH grant S10OD010610-01A1). We gratefully acknowledge W. Gutekunst, C. Haitjema, R. Behrens, J. Smith, L. Dassau and M. Raven for experimental assistance and helpful discussions. D.J.L. is grateful to the European Union for a Marie Curie Global Postdoctoral Fellowship. J.I.Y. acknowledges support from the NSF Graduate Research Fellowship. S.M. acknowledges support from Duncan and Mellichamp Chair and Cluster in Systems Biology and Bioengineering.

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Authors and Affiliations

  1. California NanoSystems Institute, University of California, Santa Barbara, 93106, California, USA

    Jia Niu & Craig J. Hawker

  2. Materials Research Laboratory, University of California, Santa Barbara, 93106, California, USA

    Jia Niu, David J. Lunn & Craig J. Hawker

  3. Department of Chemistry, University of Oxford, Oxford, OX1 3TA, UK

    David J. Lunn

  4. Department of Chemical Engineering, University of California, Santa Barbara, 93106, California, USA

    Anusha Pusuluri, Justin I. Yoo, Michelle A. O'Malley & Samir Mitragotri

  5. Center for Bioengineering, University of California, Santa Barbara, 93106, California, USA

    Samir Mitragotri & Craig J. Hawker

  6. Department of Radiology, School of Medicine, Stanford University, Stanford, 94305, California, USA

    H. Tom Soh

  7. Department of Electrical Engineering, Stanford University, Stanford, 94305, California, USA

    H. Tom Soh

  8. Department of Chemistry and Biochemistry, University of California, Santa Barbara, 93106, California, USA

    Craig J. Hawker

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Contributions

J.N., C.J.H. and H.T.S. conceived the idea and J.N. designed and performed the experiments. D.J.L. synthesized the lipidomimetic CTA compound. A.P. cultured Jurkat cells and conducted the related characterizations. J.I.Y. conducted the GPCR+ yeast culturing and related characterizations. C.J.H., H.T.S., M.A.O. and S.M. supervised the study. All authors analysed the data and co-wrote the manuscript.

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Correspondence to H. Tom Soh or Craig J. Hawker.

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Niu, J., Lunn, D., Pusuluri, A. et al. Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization. Nature Chem 9, 537–545 (2017). https://doi.org/10.1038/nchem.2713

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