#04 - Functional and Morphological Adaptation in DNA Protocells via Downstream Signal Propagation

Avik Samanta (University of Freiburg)

Tuesday, 01 Dec 21:15 - 22:00 CET

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Abstract

Title: Functional and Morphological Adaptation in DNA Protocells via Downstream Signal Propagation

Author(s): Avik Samanta^a

Affiliations: ^aUniversity of Freiburg

Abstract: The bottom-up approach in engineering artificial-protocells (PC) exhibiting dynamical behaviors and systems-based properties are emerging challenges in the field of synthetic biology [1]. The fundamental cellular processes (differentiation and morphogenesis) stem from numerous interwoven biochemical reaction pathways that instigate the physical changes in the periplasm. The capability to mimic elementary aspects of these non-equilibrium processes in protocells could pave the way towards designing life-like systems orchestrating complex spatiotemporal transformations. We unraveled a polymer-like phase-separation behavior in multiblock single-stranded DNA by triggering a nucleobase-specific lower critical solution temperature, which provides an opportunity to fabricate all-DNA hierarchical structuration with several encoded sequences for post-functionalization [2]. On the other hand, artificial metalloenzymes (ArMs) [3] emerge from anchoring an organometallic moiety within a macromolecular scaffold, and the resulting hybrid catalyst amalgamates attractive features of both homogeneous catalysts and enzymes. We used a family of genetically modified streptavidin as anchors in the PC-core to immobilize a Ru-based metathesis catalyst and performed a ring-closing metathesis to investigate the crowding effect of the environment on catalytic efficiency and stability [4]. We have also succeeded to uncage a DNA intercalating fluorophore in the course of metathesis, which eventually triggers the dynamization of the shell, resulting in morphological transformations of the PCs. Even though cross-disciplinary approaches to explore the design, structure, function, and evolutionary potential of metabolic PC with genetically evolved proteinaceous catalysts are in their early stages, our approach offers valuable insights into the achievement of chemically triggered adaptive behavior of prebiotic coacervates and towards a minimalistic design of life-like abiotic systems.

References

[1] Qiao, Yan, Mei Li, Richard Booth, and Stephen Mann. “Predatory Behaviour in Synthetic Protocell Communities.” Nature Chemistry 9, no. 2 (February 2017): 110–19. https://doi.org/10.1038/nchem.2617.

[2] Merindol, Rémi, Sebastian Loescher, Avik Samanta, and Andreas Walther. “Pathway-Controlled Formation of Mesostructured All-DNA Colloids and Superstructures.” Nature Nanotechnology 13, no. 8 (August 2018): 730–38. https://doi.org/10.1038/s41565-018-0168-1.

[3] Schwizer, Fabian, Yasunori Okamoto, Tillmann Heinisch, Yifan Gu, Michela M. Pellizzoni, Vincent Lebrun, Raphael Reuter, Valentin Köhler, Jared C. Lewis, and Thomas R. Ward. “Artificial Metalloenzymes: Reaction Scope and Optimization Strategies.” Chemical Reviews 118, no. 1 (January 10, 2018): 142–231. https://doi.org/10.1021/acs.chemrev.7b00014.

[4] Samanta, Avik, Valerio Sabatino, Thomas R. Ward, and Andreas Walther. “Functional and Morphological Adaptation in DNA Protocells via Signal Processing Prompted by Artificial Metalloenzymes.” Nature Nanotechnology 15, no. 11 (November 2020): 914–21. https://doi.org/10.1038/s41565-020-0761-y.