Universiteit Leiden

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Research project

Hybrid vesicles

Synthetic cells, also known as artificial cells or protocells, have wide ranging applications from drug delivery vectors to cell models. In biotechnology they can function as micro- or nanoreactors with possible applications in biocatalysis and photocatalysis. Phospholipids are by far the most commonly used building blocks of synthetic cells, but suffer from poor mechanical and chemical stability, impairing their applications in biotechnology. Polymersomes, which are vesicles made from amphiphilic copolymer, often exhibit much better stability, but their poor biomimetic properties limit their functionalisation with natural membrane proteins. Together with Prof. Paul Beales from the University of Leeds, we are studying whether hybrid vesicles, consisting of mixtures of (phospho)lipids and amphiphilic polymers, are suitable compartments for research in synthetic cells.

Lars Jeuken

Some membrane enzymes, like cytochrome bo3, have been shown to retain their activity for much longer when reconstituted into hybrid vesicles compared to liposomes (lipid only vesicles). Equally important, it has been observed that membrane proteins have been much easier to constitute into hybrid vesicles compared to liposomes. Together makes hybrid vesicles an exciting target for nanoreactors.

Hybrid vesicles as nanoreactors

Although several membrane proteins are now known to function well in hybrid vesicles, transporters, which transport solutes across the membrane, have not yet been tested. For synthetic cells to import or export substrates and products and thus communicate with the extravesicular environment, transporters are required. Hence, we are testing the properties of transporters in hybrid vesicles.

Key publications

Catania R., Machin J., Rappolt M., Muench S.P., Beales P.A. & Jeuken L.J.C. (2022), Detergent-free functionalization of hybrid vesicles with membrane proteins using SMALPs, Macromolecules 55: 3415-3422. DOI: acs.macromol.2c00326

Khan S., Li M., Muench S.P., Jeuken L.J.C. & Beales P.A. (2016), Durable proteo-hybrid vesicles for the extended functional lifetime of membrane proteins in bionanotechnology, Chemical Communications 52: 11020-11023. DOI: 10.1039/c6cc04207d

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