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Engineering of stimuli-responsive lipid-bilayer membranes using supramolecular systems

Abstract

The membrane proteins found in nature control many important cellular functions, including signal transduction and transmembrane ion transport, and these, in turn, are regulated by external stimuli, such as small molecules, membrane potential and light. Membrane proteins also find technological applications in fields ranging from optogenetics to synthetic biology. Synthetic supramolecular analogues have emerged as a complementary method to engineer functional membranes. This Review describes stimuli-responsive supramolecular systems developed for the control of ion transport, signal transduction and catalysis in lipid-bilayer-membrane systems. Recent advances towards achieving spatio-temporal control over activity in artificial and living cells are highlighted. Current challenges, the scope, limitations and future potential to exploit supramolecular systems for engineering stimuli-responsive lipid-bilayer membranes are discussed.

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Fig. 1: Functional lipid-bilayer membranes using stimuli-responsive supramolecular systems.
Fig. 2: Molecular recognition in lipid-bilayer membranes.
Fig. 3: Photoresponsive synthetic ion-transport systems.
Fig. 4: Ligand-gated synthetic ion channels.
Fig. 5: Mechanosensitive and voltage-sensitive transport systems.
Fig. 6: Non-equilibrium transport systems.
Fig. 7: Synthetic transmembrane signal-transduction systems.

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Acknowledgements

M.J.L. is grateful for funding through a Royal Society University Research Fellowship.

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Glossary

Transmembrane signal transduction

The transmission of molecular signals and information across a membrane, typically occurring without the signalling molecule crossing the membrane itself, maintaining cellular compartmentalization.

Stimuli-responsive supramolecular systems

Synthetic molecules or molecular assemblies that exploit intermolecular interactions for their function, and their activity is regulated by changes in their chemical or physical environment.

Mobile ion carriers

Lipid-soluble ion receptors (ionophores) that facilitate transmembrane ion transport by shuttling ions across the membrane.

Photocaging

The use of photolabile protecting groups to temporarily mask the activity of a molecule. Subsequent photoirradiation removes the protecting group to reveal the functional molecule.

Molecular photoswitches

Molecules that can be reversibly switched between at least two distinct states, which acquire different chemical and/or physical properties by absorbing photons.

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Langton, M.J. Engineering of stimuli-responsive lipid-bilayer membranes using supramolecular systems. Nat Rev Chem 5, 46–61 (2021). https://doi.org/10.1038/s41570-020-00233-6

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