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An autonomously oscillating supramolecular self-replicator

Abstract

A key goal of chemistry is to develop synthetic systems that mimic biology, such as self-assembling, self-replicating models of minimal life forms. Oscillations are often observed in complex biological networks, but oscillating, self-replicating species are unknown, and how to control autonomous supramolecular-level oscillating systems is also not yet established. Here we show how a population of self-assembling self-replicators can autonomously oscillate, so that simple micellar species repeatedly appear and disappear in time. The interplay of molecular and supramolecular events is key to observing oscillations: the repeated formation and disappearance of compartments is connected to a reaction network where molecular-level species are formed and broken down. The dynamic behaviour of our system across different length scales offers the opportunities for mass transport, as we demonstrate via reversible dye uptake. We believe these findings will inspire new biomimetic systems and may unlock nanotechnology systems such as (supra)molecular pumps, where compartment formation is controlled in time and space.

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Fig. 1: Oscillating components in the out-of-equilibrium, supramolecular reaction network.
Fig. 2: Probing the destruction reaction in the oscillating system by continuous addition of a preformed second replicator.
Fig. 3: Effect of the amount of destruction catalyst, oxidant supply and amount of thiol on the oscillations.
Fig. 4: Supramolecular oscillations can be coupled to a secondary process.

Data availability

The source data underlying Figs. 1b, 2b, 3a–e and 4 are provided as a source data file. Source data are provided with this paper.

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Acknowledgements

The authors wish to thank E. Foley for help with iSCAT measurements and L. Carrique for performing cryo-transmission electron microscopy measurements. The authors thank the ERC (Consolidator Grant, Autocat, 681491) for funding. M.G.H. thanks the EPSRC Centre for Doctoral Training in Synthesis for Biology and Medicine (EP/L015838/1) for a studentship, generously supported by AstraZeneca, Diamond Light Source, Defence Science and Technology Laboratory, Evotec, GlaxoSmithKline, Janssen, Novartis, Pfizer, Syngenta, Takeda, UCB and Vertex. This work used the OPIC electron microscopy facility which is supported by a Wellcome JIF award (060208/Z/00/Z) and a Wellcome equipment grant (093305/Z/10/Z).

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Authors

Contributions

M.G.H. and A.H.J.E. performed the experiments. R.J.H.S. performed preliminary experiments. M.G.H., A.H.J.E. and S.P.F. contributed to designing and analysing the experiments and writing and editing the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Stephen P. Fletcher.

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Nature Chemistry thanks the anonymous reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary methods and synthesis, discussion and additional data.

Supplementary Video 1

Video of the visual oscillations seen when incorporating a hydrophobic dye (250× speed). Reaction is sampled for UPLC analysis.

Supplementary Video 2

Video of the visual oscillations seen when incorporating a hydrophobic dye (duplicate reaction, 250× speed). Reaction is not sampled or disturbed.

Source data

Source Data Fig. 1

Raw numerical data for graph(s) in Figure 1

Source Data Fig. 2

Raw numerical data for graph(s) in Figure 2

Source Data Fig. 3

Raw numerical data for graph(s) in Figure 3

Source Data Fig. 4

Raw numerical data for graph(s) in Figure 4

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Howlett, M.G., Engwerda, A.H.J., Scanes, R.J.H. et al. An autonomously oscillating supramolecular self-replicator. Nat. Chem. (2022). https://doi.org/10.1038/s41557-022-00949-6

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