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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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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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.
The authors declare no competing interests.
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Supplementary Video Legends 1–5, Supplementary Notes 1–3, Supplementary Figures 1–34, Supplementary Table 1, Supplementary References 1–2
Caged prototissue spheroid
Uncaged prototissue spheroid
Prototissue spheroid undergoing reversible contractions
Prototissue undergoing reversible contractions with buckling protocells
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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