Radical polymerization inside living cells

Abstract

Polymerization reactions conducted inside cells must be compatible with the complex intracellular environment, which contains numerous molecules and functional groups that could potentially prevent or quench polymerization reactions. Here we report a strategy for directly synthesizing unnatural polymers in cells through free radical photopolymerization using a number of biocompatible acrylic and methacrylic monomers. This offers a platform to manipulate, track and control cellular behaviour by the in cellulo generation of macromolecules that have the ability to alter cellular motility, label cells by the generation of fluorescent polymers for long-term tracking studies, as well as generate a variety of nanostructures within cells. It is remarkable that free radical polymerization chemistry can take place within such complex cellular environments. This demonstration opens up a multitude of new possibilities for how chemists can modulate cellular function and behaviour and for understanding cellular behaviour in response to the generation of free radicals.

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Fig. 1: Intracellular polymerization.
Fig. 2: HeLa cells that underwent intracellular polymerization were less migratory.
Fig. 3: Actin cytoskeleton organization was altered in polymerized HeLa cells.
Fig. 4: Polymerization of NaSS in HeLa cells.
Fig. 5: Co-polymerization of HPMA with AOTCRhB in HeLa cells.
Fig. 6: Polymerization of FMMA in HeLa cells.

Data availability

All relevant data are available within the Article or the Supplementary Information.

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Acknowledgements

This work was supported by the European Research Council (advanced grant ADREEM ERC-2013-340469) and the Rosetrees Trust (A865). N.T. acknowledges support from the Commonwealth Scholarship Commission and W.L. from the Chinese Scholarship Council. The authors thank the Wellcome Trust for Multi-user Equipment Grant WT104915MA.

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J.G. and M.B. conceived, designed and directed the project. W.L. and Y.Z. conducted the control polymerizations and MTT assays. Y.Z. performed the actin experiments, Y.Z. and N.T. conducted the wound healing experiments. W.L., Y.Z. and J.C. carried out work with the fluorescent polymers. J.G., A.L. and M.B. co-wrote the manuscript. All authors analysed the data and contributed to the scientific discussion and revised the manuscript.

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Correspondence to Mark Bradley.

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Polymerized sodium 4-styrenesulfonate inside cells

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Geng, J., Li, W., Zhang, Y. et al. Radical polymerization inside living cells. Nat. Chem. 11, 578–586 (2019). https://doi.org/10.1038/s41557-019-0240-y

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