Engineering dynamic, functional membrane interfaces for artificial cells

Summary

Engineering biological systems is considered to be one of the defining technologies of the 21st century with the potential for disruptive innovations in a wide range of industry sectors. A key underpinning concept in this field is the bottom-up design and assembly of artificial cells: novel, cell-like materials with integrated biomimetic functions. This enables the engineering of artificial cells that replicate a cell’s ability to sense and respond to complex signals within their environment, utilise internal (bio)chemical computation and manufacture processes, and initiate collective responses in a community of artificial cells. To enable the full potential of engineering biology, the underpinning tools and technologies for engineering artificial cells needs to be expanded. This project will combine biological and synthetic components to create mechanically robust artificial cells that exhibit dynamic membrane-driven functions of fission (cf. cell division), fusion (cf. signal trafficking) and compartmentalisation (cf. organelle formation). The fundamental mechanisms of these processes will be studied in order to facilitate control over these dynamic processes and enable their use within the framework of engineering design. These dynamic functions will be integrated within a signalling cascade to demonstrate how these processes can be initiated as part of a signal response network in an artificial cell towards incorporating these functions within engineering biology solutions to meet industrial challenges.

We have previously contributed to the toolbox for engineering artificial cells by developing hybrid membranes with enhanced stability and durability (1,2), demonstrating new methods for functionalising membranes with integral protein nanomachines (3), designing biological (4) and synthetic, biomimetic (5,6) strategies to control dynamic structural transformations in membranes, and encapsulating feedback-controlled processes and inter-cellular signalling mechanisms (7). Future challenges lie in the integration of these approaches to create engineering biology solutions to industry challenges in sectors such as biomedical diagnostics and therapies (8), environmental remediation, clean growth and sustainable agriculture.

References:

(1) Khan S., Li M., Muench S.P., Jeuken L.J.C. and Beales P.A.; Durable Proteo-Hybrid Vesicles for the Extended Functional Lifetime of Membrane Proteins in Bionanotechnology. Chem. Commun. 52, 11020 - 11023 (2016)

(2) Seneviratne R., Coates G., Xu Z., Cornell C.E., Thompson R.F., Sadeghpour A., Maskell D.P., Jeuken L.J.C, Rappolt M. and Beales P.A.; High resolution membrane structures within hybrid lipid-polymer vesicles revealed by combining x-ray scattering and electron microscopy. Small 19, 2206267 (2023)

(3) Catania R., Machin J., Rappolt M., Muench S.P., Beales P.A. and Jeuken L.J.C.; Detergent-Free Functionalisation of Hybrid Vesicles with Membrane Proteins Using SMALPs. Macromolecules 55(9), 3415–3422 (2022)

(4) Booth A., Marklew C.J., Ciani B. and Beales P.A.; In vitro membrane remodelling by ESCRT is regulated by negative feedback from membrane tension. iScience 15, 173-184 (2019)

(5) Arribas Perez M. and Beales P.A.; Biomimetic curvature and tension-driven membrane fusion induced by silica nanoparticles. Langmuir 37(47), 13917–13931 (2021)

(6) Xu Z., Rappolt M., Tyler A.I.I. and Beales P.A.; Cubosome-Induced Topological Transformations in Giant Vesicles. ChemRxiv (2022)

(7) Miele Y., Jones S.J., Rossi F., Beales P.A. and Taylor A.F.; Collective Behavior of Urease pH Clocks in Nano- and Microvesicles Controlled by Fast Ammonia Transport. J. Phys. Chem. Lett. 13, 1979–1984 (2022)

(8) Jones S.J., Taylor A.F. and Beales P.A.; Towards feedback-controlled nanomedicines for smart, adaptive delivery. Experimental Biology and Medicine 244, 283-293 (2019)

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