Malouf, Layla;
Tanase, Diana A;
Fabrini, Giacomo;
Brady, Ryan A;
Paez-Perez, Miguel;
Leathers, Adrian;
Booth, Michael J;
(2023)
Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity.
Chem
, 9
(11)
pp. 3347-3364.
10.1016/j.chempr.2023.10.004.
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Abstract
Synthetic cells, like their biological counterparts, require internal compartments with distinct chemical and physical properties where different functionalities can be localized. Inspired by membrane-less compartmentalization in biological cells, here, we demonstrate how microphase separation can be used to engineer heterogeneous cell-like architectures with programmable morphology and compartment-targeted activity. The synthetic cells self-assemble from amphiphilic DNA nanostructures, producing core-shell condensates due to size-induced de-mixing. Lipid deposition and phase-selective etching are then used to generate a porous pseudo-membrane, a cytoplasm analog, and membrane-less organelles. The synthetic cells can sustain RNA synthesis via in vitro transcription, leading to cytoplasm and pseudo-membrane expansion caused by an accumulation of the transcript. Our approach exemplifies how architectural and functional complexity can emerge from a limited number of distinct building blocks, if molecular-scale programmability, emergent biophysical phenomena, and biochemical activity are coupled to mimic those observed in live cells.
| Type: | Article |
|---|---|
| Title: | Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.chempr.2023.10.004 |
| Publisher version: | https://doi.org/10.1016/j.chempr.2023.10.004 |
| Language: | English |
| Additional information: | © 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Synthetic cells, DNA nanotechnology, bottom-up synthetic biology, biomimetics, membrane-less organelles, phase separation, liquid-liquid phase separation, condensates, self-assembly |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10181415 |
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