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Programmed assembly of synthetic protocells into thermoresponsive prototissues

Abstract

Although several new types of synthetic cell-like entities are now available, their structural integration into spatially interlinked prototissues that communicate and display coordinated functions remains a considerable challenge. Here we describe the programmed assembly of synthetic prototissue constructs based on the bio-orthogonal adhesion of a spatially confined binary community of protein–polymer protocells, termed proteinosomes. The thermoresponsive properties of the interlinked proteinosomes are used collectively to generate prototissue spheroids capable of reversible contractions that can be enzymatically modulated and exploited for mechanochemical transduction. Overall, our methodology opens up a route to the fabrication of artificial tissue-like materials capable of collective behaviours, and addresses important emerging challenges in bottom-up synthetic biology and bioinspired engineering.

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Fig. 1: Programmed assembly of proteinosomes into synthetic prototissue spheroids.
Fig. 2: Collective contractile behaviour in prototissue spheroids.
Fig. 3: Enzyme-mediated amplitude modulation within thermoresponsive prototissue spheroids.
Fig. 4: Mechanochemical transduction within prototissue spheroids.

Data availability

The authors declare that all relevant data supporting the findings of this study are available within the paper and its Supplementary Information files. Additional data are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank NSERC Canada (PDF-487171–2016) and EU Horizon 2020 (Marie Skłodowska-Curie grant no. 701876) for funding, and the NMR/Mass Spectrometry Facility, the Wolfson Bioimaging Facility (A. Leard; BBSRC grant no. BB/L014181/1) and Chemical Imaging Facility (EPSRC grant ‘Atoms to Applications’, EP/K035746/1) for help with physical characterization. The authors also thank I. Manners, J. Finnegan and S. Briggs for assistance with GPC/DSC measurements, D. Woolfson for use of dichroism and plate reader spectrometers (BBSRC/EPSRC Bristol Synthetic Biology Research Centre, grant no. BB/L01386X/1), D. Gubala for help with AFM measurements, N. Martin and R. Booth for fruitful discussions, T. Ferrugia for assistance with the development of a customized microscope heating stage, and T. Liverpool for mathematical discussions.

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Authors

Contributions

P.G., A.J.P., M.L. and S.M. conceived the experiments. P.G. performed the experiments. P.G. and R.H. performed the force measurements. W.H.B. and P.G. developed the theoretical model for the prototissue expansion force. All authors undertook data analysis, discussed the results, and contributed to drafts of the manuscript. P.G. and S.M. wrote the final manuscript.

Corresponding author

Correspondence to Stephen Mann.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary Video Legends 1–5, Supplementary Notes 1–3, Supplementary Figures 1–34, Supplementary Table 1, Supplementary References 1–2

Reporting Summary

Supplementary Video 1

Caged prototissue spheroid

Supplementary Video 2

Uncaged prototissue spheroid

Supplementary Video 3

Prototissue spheroid undergoing reversible contractions

Supplementary Video 4

Prototissue undergoing reversible contractions with buckling protocells

Supplementary Video 5

Communication between compartments in an uncaged prototissue spheroid

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Gobbo, P., Patil, A.J., Li, M. et al. Programmed assembly of synthetic protocells into thermoresponsive prototissues. Nature Mater 17, 1145–1153 (2018). https://doi.org/10.1038/s41563-018-0183-5

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