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

ABSTRACT 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. Access through your institution Buy or subscribe This is a preview

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METABOLIC DNA PROTOCELLS Article Open access 08 July 2022 DNA-EMPOWERED SYNTHETIC CELLS AS MINIMALISTIC LIFE FORMS Article 15 May 2024 MORPHOLOGY REMODELLING AND MEMBRANE CHANNEL FORMATION

IN SYNTHETIC CELLS VIA RECONFIGURABLE DNA NANORAFTS Article Open access 13 January 2025 DATA AVAILABILITY Data for the catalysis experiments are available online. Any other data can be made

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Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS 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 * A3BMS Lab, Institute for Macromolecular Chemistry,

University of Freiburg, Freiburg, Germany Avik Samanta & Andreas Walther * DFG Cluster of Excellence “Living, Adaptive and Energy-Autonomous Materials Systems” (livMatS)@FIT, Freiburg,

Germany Avik Samanta & Andreas Walther * Freiburg Materials Research Center, University of Freiburg, Freiburg, Germany Avik Samanta & Andreas Walther * Freiburg Center for

Interactive Materials and Bioinspired Technologies (FIT), University of Freiburg, Freiburg, Germany Avik Samanta & Andreas Walther * Department of Chemistry, University of Basel, Basel,

Switzerland Valerio Sabatino & Thomas R. Ward Authors * Avik Samanta View author publications You can also search for this author inPubMed Google Scholar * Valerio Sabatino View author

publications You can also search for this author inPubMed Google Scholar * Thomas R. Ward View author publications You can also search for this author inPubMed Google Scholar * Andreas

Walther View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS 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. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION 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. PUBLISHER’S NOTE Springer Nature

remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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). https://doi.org/10.1038/s41565-020-0761-y Download citation * Received: 21 March 2020 * Accepted: 03 August 2020 *

Published: 07 September 2020 * Issue Date: November 2020 * DOI: https://doi.org/10.1038/s41565-020-0761-y SHARE THIS ARTICLE Anyone you share the following link with will be able to read

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