Dissipative self-assembly of vesicular nanoreactors


Dissipative self-assembly is exploited by nature to control important biological functions, such as cell division, motility and signal transduction. The ability to construct synthetic supramolecular assemblies that require the continuous consumption of energy to remain in the functional state is an essential premise for the design of synthetic systems with lifelike properties. Here, we show a new strategy for the dissipative self-assembly of functional supramolecular structures with high structural complexity. It relies on the transient stabilization of vesicles through noncovalent interactions between the surfactants and adenosine triphosphate (ATP), which acts as the chemical fuel. It is shown that the lifetime of the vesicles can be regulated by controlling the hydrolysis rate of ATP. The vesicles sustain a chemical reaction but only as long as chemical fuel is present to keep the system in the out-of-equilibrium state. The lifetime of the vesicles determines the amount of reaction product produced by the system.

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Figure 1: Formation and characterization of vesicles.
Figure 2: Transient formation of vesicles.
Figure 3: Product formation as a function of vesicle lifetime.


  1. 1

    Kushner, D. J. Self-assembly of biological structures. Bacteriol. Rev. 33, 302–245 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2

    Gale, P. A. & Steed, J. W. (eds) Self-assembly and Supramolecular Devices (Supramolecular Chemistry: From Molecules to Nanomaterials Vol. 5, Wiley, 2012).

    Google Scholar 

  3. 3

    Mattia, E. & Otto, S. Supramolecular systems chemistry. Nature Nanotech. 10, 111–119 (2015).

    CAS  Article  Google Scholar 

  4. 4

    Karsenti, E. Self-organization in cell biology: a brief history. Nature Rev. Mol. Cell Biol. 9, 255–262 (2008).

    CAS  Article  Google Scholar 

  5. 5

    Whitesides, G. M. & Ismagilov, R. F. Complexity in chemistry. Science 284, 89–92 (1999).

    CAS  Article  Google Scholar 

  6. 6

    Fialkowski, M. et al. Principles and implementations of dissipative (dynamic) self-assembly. J. Phys. Chem. B 110, 2482–2496 (2006).

    CAS  Article  Google Scholar 

  7. 7

    Desai, A. & Mitchison, T. J. Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13, 83–117 (1997).

    CAS  Article  Google Scholar 

  8. 8

    Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, 2001).

    Google Scholar 

  9. 9

    Rizzoli, S. O. Synaptic vesicle recycling: steps and principles. EMBO J. 33, 788–822 (2014).

    CAS  Article  Google Scholar 

  10. 10

    Fletcher, S. P., Dumur, F., Pollard, M. M. & Feringa, B. L. A reversible, unidirectional molecular rotary motor driven by chemical energy. Science 310, 80–82 (2005).

    CAS  Article  Google Scholar 

  11. 11

    Ragazzon, G., Baroncini, M., Silvi, S., Venturi, M. & Credi, A. Light-powered autonomous and directional molecular motion of a dissipative self-assembling system. Nature Nanotech. 10, 70–75 (2015).

    CAS  Article  Google Scholar 

  12. 12

    Cheng, C. et al. Energetically demanding transport in a supramolecular assembly. J. Am. Chem. Soc. 136, 14702–14705 (2014).

    CAS  Article  Google Scholar 

  13. 13

    Cheng, C. et al. An artificial molecular pump. Nature Nanotech. 10, 547–553 (2015).

    CAS  Article  Google Scholar 

  14. 14

    Dambenieks, A. K., Vu, P. H. Q. & Fyles, T. M. Dissipative assembly of a membrane transport system. Chem. Sci. 5, 3396–3403 (2014).

    CAS  Article  Google Scholar 

  15. 15

    Krabbenborg, S. O., Veerbeek, J. & Huskens, J. Spatially controlled out-of-equilibrium host–guest system under electrochemical control. Chem. Eur. J. 21, 9638–9644 (2015).

    CAS  Article  Google Scholar 

  16. 16

    Boekhoven, J. et al. Dissipative self-assembly of a molecular gelator by using a chemical fuel. Angew. Chem. Int. Ed. 49, 4825–4828 (2010).

    CAS  Article  Google Scholar 

  17. 17

    Boekhoven, J., Hendriksen, W. E., Koper, G. J. M., Eelkema, R. & van Esch, J. H. Transient assembly of active materials fueled by a chemical reaction. Science 349, 1075–1079 (2015).

    CAS  Article  Google Scholar 

  18. 18

    Debnath, S., Roy, S. & Ulijn, R. V. Peptide nanofibers with dynamic instability through nonequilibrium biocatalytic assembly. J. Am. Chem. Soc. 135, 16789–16792 (2013).

    CAS  Article  Google Scholar 

  19. 19

    Pappas, C. G., Sasselli, I. R. & Ulijn, R. V. Biocatalytic pathway selection in transient tripeptide nanostructures. Angew. Chem. Int. Ed. 54, 8119–8123 (2015).

    CAS  Article  Google Scholar 

  20. 20

    Aida, T., Meijer, E. W. & Stupp, S. I. Functional supramolecular polymers. Science 335, 813–817 (2012).

    CAS  Article  Google Scholar 

  21. 21

    Warren, S. C., Guney-Altay, O. & Grzybowski, B. A. Responsive and nonequilibrium nanomaterials. J. Phys. Chem. Lett. 3, 2103–2111 (2012).

    CAS  Article  Google Scholar 

  22. 22

    Pezzato, C. & Prins, L. J. Transient signal generation in a self-assembled nanosystem fueled by ATP. Nature Commun. 6, 7790 (2015).

    CAS  Article  Google Scholar 

  23. 23

    Sasaki, R. & Murata, S. Aggregation of amphiphilic pyranines in water: facile micelle formation in the presence of methylviologen. Langmuir 24, 2387–2394 (2008).

    CAS  Article  Google Scholar 

  24. 24

    Koestereli, Z. & Severin, K. Fluorescence sensing of spermine with a frustrated amphiphile. Chem. Commun. 48, 5841–5843 (2012).

    CAS  Article  Google Scholar 

  25. 25

    Li, G., Zhang, S., Wu, N., Cheng, Y. & You, J. Spontaneous counterion-induced vesicle formation: multivalent binding to europium(III) for a wide-range optical pH sensor. Adv. Funct. Mater. 24, 6204–6209 (2014).

    CAS  Article  Google Scholar 

  26. 26

    Prins, L. J. Emergence of complex chemistry on an organic monolayer. Acc. Chem. Res. 48, 1920–1928 (2015).

    CAS  Article  Google Scholar 

  27. 27

    Cruz-Campa, I. et al. A novel class of metal-directed supramolecular DNA-delivery systems. Chem. Commun. 2944–2946 (2007).

  28. 28

    Heuser, T., Steppert, A.-K., Molano Lopez, C., Zhu, B. & Walther, A. Generic concept to program the time domain of self-assemblies with a self-regulation mechanism. Nano Lett. 15, 2213–2219 (2015).

    CAS  Article  Google Scholar 

  29. 29

    Walde, P., Umakoshi, H., Stano, P. & Mavelli, F. Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators. Chem. Commun. 50, 10177–10197 (2014).

    CAS  Article  Google Scholar 

  30. 30

    Galinier, F., Bertorelle, F. & Fery-Forgues, S. Spectrophotometric study of the incorporation of NBD probes in micelles: is a long alkyl chain on the fluorophore an advantage? C.R. Acad. Sci. Chim. 4, 941–950 (2001).

    CAS  Google Scholar 

  31. 31

    Zhang, X. C., Jackson, J. K. & Burt, H. M. Determination of surfactant critical micelle concentration by a novel fluorescence depolarization technique. J. Biochem. Biophys. Methods 31, 145–150 (1996).

    CAS  Article  Google Scholar 

  32. 32

    Yu, L., Zhang, H. & Ding, J. D. A subtle end-group effect on macroscopic physical gelation of triblock copolymer aqueous solutions. Angew. Chem. Int. Ed. 45, 2232–2235 (2006).

    CAS  Article  Google Scholar 

  33. 33

    Ryabov, Y. E., Geraghty, C., Varshney, A. & Fushman, D. An efficient computational method for predicting rotational diffusion tensors of globular proteins using an ellipsoid representation. J. Am. Chem. Soc. 128, 15432–15444 (2006).

    CAS  Article  Google Scholar 

  34. 34

    Chattoraj, S., Chowdhury, R., Ghosh, S. & Bhattacharyya, K. Heterogeneity in binary mixtures of dimethyl sulfoxide and glycerol: fluorescence correlation spectroscopy. J. Chem. Phys. 138, 214507 (2013).

    Article  Google Scholar 

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This work was financially supported by the European Commission (grant MSCA 657486 to S.M.), COST Action CM1304 (to L.J.P.), the University of Padova (grant CPDA138148 to L.J.P.) and the Italian Ministry of Education and Research (grant PRIN2010C4R8M8 to C.F.). Full data are provided in the Supplementary Information. ESEM measurements were performed by C. Furlan at the CE.A.S.C. at the University of Padova. CryoTEM measurements were performed by E. Paccagnini in the Electron Microscopy Laboratory of the Department of Life Sciences at the University of Siena (director, P. Lupetti). The authors thank J. Chen for a critical assessment of the manuscript, M. Zerbetto for discussions on the FCS analysis and M. Zangrossi for preparation of the movies.

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S.M. and L.J.P. designed the experiments. S.M. performed all experiments, except for the FCS and confocal microscopy studies, which were performed by I.F. L.J.P. wrote models T, K1 and K2 and performed fitting and simulations. C.F. and P.S. were involved in data interpretation. L.J.P. wrote the manuscript and all authors commented on it.

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Correspondence to Leonard J. Prins.

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The authors declare no competing financial interests.

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Maiti, S., Fortunati, I., Ferrante, C. et al. Dissipative self-assembly of vesicular nanoreactors. Nature Chem 8, 725–731 (2016). https://doi.org/10.1038/nchem.2511

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