Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Predatory behaviour in synthetic protocell communities

Abstract

Recent progress in the chemical construction of colloidal objects comprising integrated biomimetic functions is paving the way towards rudimentary forms of artificial cell-like entities (protocells). Although several new types of protocells are currently available, the design of synthetic protocell communities and investigation of their collective behaviour has received little attention. Here we demonstrate an artificial form of predatory behaviour in a community of protease-containing coacervate microdroplets and protein–polymer microcapsules (proteinosomes) that interact via electrostatic binding. The coacervate microdroplets act as killer protocells for the obliteration of the target proteinosome population by protease-induced lysis of the protein–polymer membrane. As a consequence, the proteinosome payload (dextran, single-stranded DNA, platinum nanoparticles) is trafficked into the attached coacervate microdroplets, which are then released as functionally modified killer protocells capable of rekilling. Our results highlight opportunities for the development of interacting artificial protocell communities, and provide a strategy for inducing collective behaviour in soft matter microcompartmentalized systems and synthetic protocell consortia.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Design and construction of a predator/prey synthetic protocell community.
Figure 2: FACS analysis of predatory behaviour in binary protocell populations.
Figure 3: Coacervate-microdroplet-mediated proteinosome disassembly and payload transfer.
Figure 4: DNA trafficking in binary protocell populations.
Figure 5: Extraction, transfer and capture of inorganic catalysts by coacervate-microdroplet-mediated proteinosome disassembly.

References

  1. 1

    Huang, X., Patil, A. J., Li, M. & Mann, S. Design and construction of higher-order structure and function in proteinosome-based protocells. J. Am. Chem. Soc. 136, 9225–9234 (2014).

    CAS  Article  Google Scholar 

  2. 2

    Renggli, K. et al. Selective and responsive nanoreactors. Adv. Funct. Mater. 21, 1241–1259 (2011).

    CAS  Article  Google Scholar 

  3. 3

    Stäedler, B. et al. Polymer hydrogel capsules: en route toward synthetic cellular systems. Nanoscale 1, 68–73 (2009).

    Article  Google Scholar 

  4. 4

    Caschera, F. & Noireaux, V. Integration of biological parts toward the synthesis of a minimal cell. Curr. Opin. Chem. Biol. 22, 85–91 (2014).

    CAS  Article  Google Scholar 

  5. 5

    Li, M., Huang, X., Tang, T. Y. D. & Mann, S. Synthetic cellularity based on non-lipid micro-compartments and protocell models. Curr. Opin. Chem. Biol. 22, 1–11 (2014).

    Article  Google Scholar 

  6. 6

    Miller, D. M. & Gulbis, J. M. Engineering protocells prospects for self-assembly and nanoscale production-lines. Life 5, 1019–1053 (2015).

    CAS  Article  Google Scholar 

  7. 7

    Nourian, Z. & Danelon, C. Linking genotype and phenotype in protein synthesizing liposomes with external supply of resources. ACS Synth. Biol. 2, 186–193 (2013).

    CAS  Article  Google Scholar 

  8. 8

    Martini, L. & Mansy, S. S. Cell-like systems with riboswitch controlled gene expression. Chem. Commun. 47, 10734–10736 (2011).

    CAS  Article  Google Scholar 

  9. 9

    Peters, R. J. et al. Cascade reactions in multicompartmentalized polymersomes. Angew. Chem. Int. Ed. 53, 146–150 (2014).

    CAS  Article  Google Scholar 

  10. 10

    Peters, R. J. R. W., Louzao, I. & van Hest, J. C. M. From polymeric nanoreactors to artificial organelles. Chem. Sci. 3, 335–342 (2012).

    CAS  Article  Google Scholar 

  11. 11

    Keating, C. D. Aqueous phase separation as a possible route to compartmentalization of biological molecules. Acc. Chem. Res. 45, 2114–2124 (2012).

    CAS  Article  Google Scholar 

  12. 12

    Dominak, L. M., Omiatek, D. M., Gundermann, E. L., Heien, M. L. & Keating, C. D. Polymeric crowding agents improve passive biomacromolecule encapsulation in lipid vesicles. Langmuir 26, 13195–13200 (2010).

    CAS  Article  Google Scholar 

  13. 13

    Chandrawati, R. & Caruso, F. Biomimetic liposome- and polymersome-based multicompartmentalized assemblies. Langmuir 28, 13798–13807 (2012).

    CAS  Article  Google Scholar 

  14. 14

    Chandrawati, R. et al. Engineering advanced capsosomes: maximizing the number of subcompartments, cargo retention, and temperature-triggered reaction. ACS Nano 4, 1351–1361 (2010).

    CAS  Article  Google Scholar 

  15. 15

    Torre, P., Keating, C. D. & Mansy, S. S. Aqueous multi-phase systems within water-in-oil emulsion droplets for the construction of genetically encoded cellular mimics. Langmuir 30, 5695–5699 (2014).

    CAS  Article  Google Scholar 

  16. 16

    Tawfik, D. S. & Griffiths, A. D. Man-made cell-like compartments for molecular evolution. Nat. Biotechnol. 16, 652–656 (1998).

    CAS  Article  Google Scholar 

  17. 17

    Li, M., Harbron, R. L., Weaver, J. V. M., Binks, B. P. & Mann, S. Electrostatically gated membrane permeability in inorganic protocells. Nat. Chem. 5, 529–536 (2013).

    CAS  Article  Google Scholar 

  18. 18

    Huang, X. et al. Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells. Nat. Commun. 4, 2239 (2013).

    Article  Google Scholar 

  19. 19

    Koga, S., Williams, D. S., Perriman, A. W. & Mann, S. Peptide-nucleotide microdroplets as a step towards a membrane-free protocell model. Nat. Chem. 3, 720–724 (2011).

    CAS  Article  Google Scholar 

  20. 20

    Fothergill, J., Li, M., Davis, S. A., Cunningham, J. A. & Mann, S. Nanoparticle-based membrane assembly and silicification in coacervate microdroplets as a route to complex colloidosomes. Langmuir 30, 14591–14596 (2014).

    CAS  Article  Google Scholar 

  21. 21

    Williams, D. S., Patil, A. J. & Mann, S. Spontaneous structuration in coacervate-based protocells by polyoxometalate-mediated membrane assembly. Small 10, 1830–1840 (2014).

    CAS  Article  Google Scholar 

  22. 22

    Tang, T. Y. D. et al. Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. Nat. Chem. 6, 527–533 (2014).

    Article  Google Scholar 

  23. 23

    Huang, X., Li, M. & Mann, S. Membrane-mediated cascade reactions in enzyme–polymer proteinosomes. Chem. Commun. 50, 6278–6280 (2014).

    CAS  Article  Google Scholar 

  24. 24

    van Swaay, D., Tang, T.-Y.D., Mann, S. & deMello, A. Microfluidic formation of membrane-free aqueous coacervate droplets in water. Angew. Chem. Int. Ed. 54, 8398–8401 (2015).

    CAS  Article  Google Scholar 

  25. 25

    Tang, T.-Y.D., van Swaay, D., deMello, A., Anderson, J. L. R. & Mann, S. In vitro gene expression within membrane-free coacervate protocells. Chem. Commun. 51, 11429–11432 (2015).

    Article  Google Scholar 

  26. 26

    Crosby, J. et al. Stabilization and enhanced reactivity of actinorhodin polyketide synthase minimal complex in polymer/nucleotide coacervate droplets. Chem. Commun. 48, 11832–11834 (2012).

    CAS  Article  Google Scholar 

  27. 27

    Yin, Y. et al. Electric field excitation and non-equilibrium dynamics in polypeptide/DNA synthetic protocells. Nat. Commun. 7, 10658 (2016).

    CAS  Article  Google Scholar 

  28. 28

    Stano, P. & Luisi, P. L. Semi-synthetic minimal cells origin and recent developments. Curr. Opin. Biotechnol. 24, 633–638 (2013).

    CAS  Article  Google Scholar 

  29. 29

    Goff, L. L. & Lecuit, T. Phase transition in a cell. Science 324, 1654–1655 (2009).

    Article  Google Scholar 

  30. 30

    Hammer, D. A. & Kamat, N. P. Towards an artificial cell. FEBS Lett. 586, 2882–2890 (2012).

    CAS  Article  Google Scholar 

  31. 31

    Pohorille, A. & Deamer, D. Artificial cells prospects for biotechnology. Trends Biotechnol. 20, 123–128 (2002).

    CAS  Article  Google Scholar 

  32. 32

    Gardner, P. M., Winzer, K. & Davis, B. G. Sugar synthesis in a protocellular model leads to a cell signalling response in bacteria. Nat. Chem. 1, 377–383 (2009).

    CAS  Article  Google Scholar 

  33. 33

    Lentini, R. et al. Integrating artificial with natural cells to translate chemical messages that direct E. coli behaviour. Nat. Commun. 5, 4012 (2014).

    CAS  Article  Google Scholar 

  34. 34

    Weitz, M. et al. Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator. Nat. Chem. 6, 295–302 (2014).

    CAS  Article  Google Scholar 

  35. 35

    Schwarz-Schilling, M., Aufinger, L., Muckl, A. & Simmel, F. C. Chemical communication between bacteria and cell-free gene expression systems within linear chains of emulsion droplets. Integr. Biol. 8, 564–570 (2016).

    CAS  Article  Google Scholar 

  36. 36

    Sun, S. et al. Chemical signaling and functional activation in colloidosome-based protocells. Small 12, 1920–1927 (2016).

    CAS  Article  Google Scholar 

  37. 37

    Rollie, S., Mangold, M. & Sundmacher, K. Designing biological systems: systems engineering meets synthetic biology. Chem. Eng. Sci. 69, 1–29 (2012).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank the Engineering and Physical Sciences Research Council (UK) and European Research Council (Advanced Grant) for financial support. We thank A. Patil, A. Perriman and X. Huang for fruitful discussions, A. Leard and K. Jepson for assistance with confocal microscopy, and A. Herman and S. Chappell for assistance with FACS.

Author information

Affiliations

Authors

Contributions

Y.Q., M.L. and S.M. conceived the experiments, Y.Q. and R.B. performed the experiments, Y.Q. and M.L. undertook the data analysis and Y.Q., M.L. and S.M. wrote the manuscript.

Corresponding author

Correspondence to Stephen Mann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary information (PDF 16343 kb)

Supplementary information

Supplementary Movie 1 (MOV 637 kb)

Supplementary information

Supplementary Movie 2 (MOV 2076 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Qiao, Y., Li, M., Booth, R. et al. Predatory behaviour in synthetic protocell communities. Nature Chem 9, 110–119 (2017). https://doi.org/10.1038/nchem.2617

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing