DNA-programmed nanogels as dynamic membraneless compartments for synthetic cells
- 1Department of Chemistry, University College London, 20 Gordon Street, London, U.K., WC1H 0AJ
Abstract
Bottom-up synthetic biology aims to engineer minimal systems that mimic and expand upon biological structures and functions. Programmed and dynamic organisation of intracellular components into membraneless organelles is being uncovered as vital to many cellular processes. Current approaches to introduce such membraneless compartmentalisation into bottom-up synthetic cells have focused on biomolecular coacervates, which are generally highly sensitive to environmental conditions and limited in their ability to controllably interact. A major benefit of synthetic cells, over living cellular systems, is that non-biological components can be incorporated to expand their functionality. Here, we present DNA-coated nanogels as a new membraneless compartment that can be interfaced with vesicle membranes in a dynamic and programmed manner. Nanogels are well-defined nanoscale cross-linked polymer networks. The selection of the constituent polymers gives rise to tuneable size, excellent biostability, stimuli-responsiveness, and versatile cargo loading. The ability to covalently and non-covalently load a wide variety of cargoes into nanogels has led to them being widely investigated as drug-delivery devices and nanoreactors. By functionalising nanogels with DNA, we achieved specific assembly and localisation of the nanogels onto DNA-coated vesicle membranes, creating a new type of synthetic cell. We then achieved selective disassembly and release of the DNA-nanogels by using enzymatic and DNA triggers. This approach introduces DNA-nanogels as a new membraneless platform to dynamically control the compartmentalisation state of synthetic cells. Combined with nanogel biocompatibility and loading capacity, DNAnanogels might be exploited to spatiotemporally organise biomolecular reactions and introduce entirely new functions to synthetic cells.
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BibTeX
@misc{bradic2026dnaprogrammed,
title = {{DNA-programmed nanogels as dynamic membraneless compartments for synthetic cells}},
author = {Ina Bradic and Chelsea Dack and Ellen Parkes and Michael J. Booth},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010597/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010597/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - DNA-programmed nanogels as dynamic membraneless compartments for synthetic cells
AU - Ina Bradic
AU - Chelsea Dack
AU - Ellen Parkes
AU - Michael J. Booth
PY - 2026
DA - 2026/10/16
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010597/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010597/v1
AB - Bottom-up synthetic biology aims to engineer minimal systems that mimic and expand upon biological structures and functions. Programmed and dynamic organisation of intracellular components into membraneless organelles is being uncovered as vital to many cellular processes. Current approaches to introduce such membraneless compartmentalisation into bottom-up synthetic cells have focused on biomolecular coacervates, which are generally highly sensitive to environmental conditions and limited in their ability to controllably interact. A major benefit of synthetic cells, over living cellular systems, is that non-biological components can be incorporated to expand their functionality. Here, we present DNA-coated nanogels as a new membraneless compartment that can be interfaced with vesicle membranes in a dynamic and programmed manner. Nanogels are well-defined nanoscale cross-linked polymer networks. The selection of the constituent polymers gives rise to tuneable size, excellent biostability, stimuli-responsiveness, and versatile cargo loading. The ability to covalently and non-covalently load a wide variety of cargoes into nanogels has led to them being widely investigated as drug-delivery devices and nanoreactors. By functionalising nanogels with DNA, we achieved specific assembly and localisation of the nanogels onto DNA-coated vesicle membranes, creating a new type of synthetic cell. We then achieved selective disassembly and release of the DNA-nanogels by using enzymatic and DNA triggers. This approach introduces DNA-nanogels as a new membraneless platform to dynamically control the compartmentalisation state of synthetic cells. Combined with nanogel biocompatibility and loading capacity, DNAnanogels might be exploited to spatiotemporally organise biomolecular reactions and introduce entirely new functions to synthetic cells.
ER -