%0 Journal Article
%@ 2451-9294
%A Malouf, Layla
%A Tanase, Diana A
%A Fabrini, Giacomo
%A Brady, Ryan A
%A Paez-Perez, Miguel
%A Leathers, Adrian
%A Booth, Michael J
%A Di Michele, Lorenzo
%D 2023
%F discovery:10181415
%I Elsevier BV
%J Chem
%K Synthetic cells, DNA nanotechnology, bottom-up synthetic biology, biomimetics, membrane-less organelles, phase separation, liquid-liquid phase separation, condensates, self-assembly
%N 11
%P 3347-3364
%T Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity
%U https://discovery.ucl.ac.uk/id/eprint/10181415/
%V 9
%X 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.
%Z © 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/).