Approaches Towards Synthetic Signal Transduction in Phospholipid Bilayers

della Sala, Flavio; Tilly, David P.; Webb, Simon J.

doi:10.1007/978-3-030-57456-7_1

Flavio della Sala^4,5,
David P. Tilly^4,5 &
Simon J. Webb^4,5

883 Accesses
1 Citations
2 Altmetric

Abstract

Synthetic signal transduction is an exciting new research field that applies supramolecular chemistry in a membrane environment to provide insight into the physical processes involved in natural signal transduction and to open new opportunities in synthetic biology, for example the integration of artificial signaling pathways into cells. Although it is still a developing field, we discuss a selection of recent stimuli-responsive supramolecular constructs that, when embedded in the phospholipid bilayer, can mimic aspects of the behavior of different natural signaling proteins, including ligand-gated ion channels, G-protein coupled receptors and receptor tyrosine kinases. The lipid bilayer plays a key part in these biomimetic systems, as this complex anisotropic environment provides challenges both when designing supramolecular systems that function in the bilayer and when analyzing the data they provide. Nonetheless these recent studies have provided key insights into how the bilayer affects binding to, the conformation of, and catalysis by membrane-embedded supramolecular constructs. If successful, these model systems promise to be key components for bottom-up synthetic biology, the creation of artificial cells and devices starting from molecular components.

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Abbreviations

Aib:: α-amino-iso-butyric acid
ATP:: adenosine triphosphate
CFTR:: cystic fibrosis transmembrane conductance regulator
DET:: diethylenetriamine
DMPC:: 1,2-dimyristoyl-sn-glycero-3-phosphocholine
DNA:: deoxyribonucleic acid
DOPC:: 1,2-dioleoyl-sn-glycero-3-phosphocholine
DOPE:: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
DPPC:: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
E/M :: excimer/monomer
EDTA:: ethylenediaminetetraacetic acid
EGFR:: epidermal growth factor receptor
FRET:: Förster resonance energy transfer
GABA:: γ-aminobutyric acid
GDP:: guanosine diphosphate
GPCR:: G-protein coupled receptor
GTP:: guanosine triphosphate
h.e.:: helical excess
HPTS:: 8-hydroxypyrene-1,3,6-trisulfonic acid
HRE:: hormone responsive element
IR:: insulin receptor
nAChR:: nicotinic acetylcholine receptor
NMR:: nuclear magnetic resonance
PA:: 2-phenethylamine
PBC:: planar bilayer conductance
pLGIC:: pentameric ligand-gated ion channel
RTK:: receptor tyrosine kinase
SHR:: steroid hormone receptor
ss-NMR:: solid state nuclear magnetic resonance

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Acknowledgements

FDS, DPT and SJW thank the EPSRC (grant EP/P027067/1) for financial support.

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School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
Flavio della Sala, David P. Tilly & Simon J. Webb
Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK
Flavio della Sala, David P. Tilly & Simon J. Webb

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Flavio della Sala
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David P. Tilly
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Simon J. Webb
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SupraChem Lab, "Petru Poni" Institute of Macromolecular Chemistry, Iasi, Romania
Marc J.M. Abadie
SupraChem Lab, "Petru Poni" Institute of Macromolecular Chemistry, Iasi, Romania
Mariana Pinteala
SupraChem Lab, "Petru Poni" Institute of Macromolecular Chemistry, Iasi, Romania
Alexandru Rotaru

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della Sala, F., Tilly, D.P., Webb, S.J. (2021). Approaches Towards Synthetic Signal Transduction in Phospholipid Bilayers. In: J.M. Abadie, M., Pinteala, M., Rotaru, A. (eds) New Trends in Macromolecular and Supramolecular Chemistry for Biological Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-57456-7_1

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