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Placing and shaping liposomes with reconfigurable DNA nanocages

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Abstract

The diverse structure and regulated deformation of lipid bilayer membranes are among a cell's most fascinating features. Artificial membrane-bound vesicles, known as liposomes, are versatile tools for modelling biological membranes and delivering foreign objects to cells. To fully mimic the complexity of cell membranes and optimize the efficiency of delivery vesicles, controlling liposome shape (both statically and dynamically) is of utmost importance. Here we report the assembly, arrangement and remodelling of liposomes with designer geometry: all of which are exquisitely controlled by a set of modular, reconfigurable DNA nanocages. Tubular and toroid shapes, among others, are transcribed from DNA cages to liposomes with high fidelity, giving rise to membrane curvatures present in cells yet previously difficult to construct in vitro. Moreover, the conformational changes of DNA cages drive membrane fusion and bending with predictable outcomes, opening up opportunities for the systematic study of membrane mechanics.

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Figure 1: Organizing liposomes with DNA nanocages.
Figure 2: Templated assembly of width-defined membrane tubules.
Figure 3: Generating membrane structures with complex curvature.
Figure 4: Dynamic control of liposome shape by DNA template reconfiguration.

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Change history

  • 22 November 2017

    In the original version of this Article, the name of co-author Marc C. Llaguno was coded erroneously, resulting in it being incorrect when exported to citation databases. This has now been corrected, though no changes will be visible.

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Acknowledgements

The authors thank J. T. Powell for proofreading the manuscript and D. K. Toomre and T. J. Melia for discussion. This work is supported by a National Institutes of Health (NIH) Director's New Innovator Award (DP2-GM114830), an NIH grant (R21-GM109466), and a Yale University faculty startup fund to C.L. and an European Research Council (ERC) funded grant under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 669612) to F.P.

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Contributions

Z.Z. initiated the project, designed and carried out most of the experiments, analysed the data, and prepared most of the manuscript. Y.Y. performed cryo-EM study and prepared the manuscript. F.P. modelled energy input for membrane fusion and prepared the manuscript. M.C.L. performed tomography study, analysed the data, and prepared the manuscript. C.L. initiated the project, designed and supervised the study, interpreted the data, and prepared the manuscript. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Chenxiang Lin.

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The authors declare no competing financial interests.

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Zhang, Z., Yang, Y., Pincet, F. et al. Placing and shaping liposomes with reconfigurable DNA nanocages. Nature Chem 9, 653–659 (2017). https://doi.org/10.1038/nchem.2802

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