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Functional and morphological adaptation in DNA protocells via signal processing prompted by artificial metalloenzymes


For life to emerge, the confinement of catalytic reactions within protocellular environments has been proposed to be a decisive aspect to regulate chemical activity in space1. Today, cells and organisms adapt to signals2,3,4,5,6 by processing them through reaction networks that ultimately provide downstream functional responses and structural morphogenesis7,8. Re-enacting such signal processing in de novo-designed protocells is a profound challenge, but of high importance for understanding the design of adaptive systems with life-like traits. We report on engineered all-DNA protocells9 harbouring an artificial metalloenzyme10 whose olefin metathesis activity leads to downstream morphogenetic protocellular responses with varying levels of complexity. The artificial metalloenzyme catalyses the uncaging of a pro-fluorescent signal molecule that generates a self-reporting fluorescent metabolite designed to weaken DNA duplex interactions. This leads to pronounced growth, intraparticular functional adaptation in the presence of a fluorescent DNA mechanosensor11 or interparticle protocell fusion. Such processes mimic chemically transduced processes found in cell adaptation and cell-to-cell adhesion. Our concept showcases new opportunities to study life-like behaviour via abiotic bioorthogonal chemical and mechanical transformations in synthetic protocells. Furthermore, it reveals a strategy for inducing complex behaviour in adaptive and communicating soft-matter microsystems, and it illustrates how dynamic properties can be upregulated and sustained in micro-compartmentalized media.

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Fig. 1: Design concept, strategy and system behaviour of ArM-catalysed signal conversion and downstream adaptation inside all-DNA PCs.
Fig. 2: Compartment-selective functionalization of PCs.
Fig. 3: Intraprotocellular RCM of Subs-I and Subs-II catalysed by genetically engineered ArMs.
Fig. 4: CLSM monitoring of ArM-catalysed RCM inside PCs and ensuing morphological transformations.
Fig. 5: RCM-induced, self-reporting, downstream functional adaptation and morphological output.

Data availability

Data for the catalysis experiments are available online. Any other data can be made available upon reasonable request to the corresponding authors. Source data are provided with this paper.


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We acknowledge the support by the European Research Council starting grant to A.W. (TimeProSAMat (agreement 677960)) and advanced grant to T.R.W. (DrEAM, agreement 694424), the DFG Cluster of Excellence livMatS “Living, Adaptive and Energy-Autonomous Materials Systems” and the NCCR Molecular Systems Engineering. A.S. acknowledges the support by the Alexander von Humboldt Foundation.

Author information

Authors and Affiliations



A.S. and A.W. conceived the project. A.S., V.S., A.W. and T.R.W. designed and performed all the experiments. A.S. analysed the data and prepared the preliminary draft. A.W. and T.R.W supervised the project. All the authors contributed to writing the manuscript.

Corresponding authors

Correspondence to Thomas R. Ward or Andreas Walther.

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The authors declare no competing interests.

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Peer review information Nature Nanotechnology thanks Tom de Greef and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–11, Tables 1 and 2, Notes 1 and 2 and refs 1–4.

Supplementary Video 1

Fluorescence recovery after successive photobleaching in the case of pristine PCs.

Supplementary Video 2

Fluorescence recovery after photobleaching in the case of streptavidin-loaded protocells.

Source data

Source Data Fig. 3

Metathesis kinetics, mutant screenings and crowding.

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Samanta, A., Sabatino, V., Ward, T.R. et al. Functional and morphological adaptation in DNA protocells via signal processing prompted by artificial metalloenzymes. Nat. Nanotechnol. 15, 914–921 (2020).

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