Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity

DOI: 10.1016/j.chempr.2023.10.004
Data DOI: 10.17863/CAM.101613

Authors: Layla Malouf (University of Cambridge; Imperial College London) , Diana A. Tanase (University of Cambridge; Imperial College London) , Giacomo Fabrini (Imperial College London) , Ryan A. Brady (St. Jude Children’s Research Hospital) , Miguel Paez-Perez (Imperial College London) , Adrian Leathers (University of Cambridge) , Michael J. Booth (University College London) , Lorenzo Di Michele (University of Cambridge; Imperial College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chem , VOL 210

State: Published (Approved)
Published: November 2023
Diamond Proposal Number(s): 29072

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.

Subject Areas: Chemistry, Materials, Biology and Bio-materials


Instruments: I22-Small angle scattering & Diffraction

Added On: 08/11/2023 11:36

Documents:
1-s2.0-S2451929423005119-main.pdf

Discipline Tags:

Biotechnology Biochemistry Chemistry Materials Science Chemical Engineering Engineering & Technology Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)