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Controlled membrane translocation provides a mechanism for signal transduction and amplification

Nature Chemistry volume 9, pages 426–430 (2017)Cite this article

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Abstract

Transmission and amplification of chemical signals across lipid bilayer membranes is of profound significance in many biological processes, from the development of multicellular organisms to information processing in the nervous system. In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, and signal transduction is often associated with an amplified signalling cascade. The ability to reproduce such processes in artificial systems has potential applications in sensing, controlled drug delivery and communication between compartments in tissue-like constructs of synthetic vesicles. Here we describe a mechanism for transmitting a chemical signal across a membrane based on the controlled translocation of a synthetic molecular transducer from one side of a lipid bilayer membrane to the other. The controlled molecular motion has been coupled to the activation of a catalyst on the inside of a vesicle, which leads to a signal-amplification process analogous to the biological counterpart.

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Figure 1: Mechanisms of transmembrane signal transduction.
Figure 2: Membrane translocation as a signal-transduction mechanism.
Figure 3: Transmembrane signal transduction.
Figure 4: Transmembrane signal amplification and reversible switching of catalysis.

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Acknowledgements

We thank the University of Cambridge Oppenheimer Fund for an Early Career Research Fellowship (M.J.L.), the Wiener-Anspach Foundation for a postdoctoral fellowship (F.K.) and F. Kundel and D. Klenerman for the TIRFM imaging experiments.

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Authors and Affiliations

  1. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    Matthew J. Langton, Flore Keymeulen, Maria Ciaccia & Christopher A. Hunter

  2. Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK

    Nicholas H. Williams

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  1. Matthew J. Langton
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  2. Flore Keymeulen
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Contributions

M.J.L., F.K. and M.C. carried out the experimental work. N.H.W. and C.A.H. supervised the project. All the authors contributed to the experimental design, analysis of the results and discussion of the manuscript. M.J.L., F.K., N.H.W. and C.A.H. wrote the paper.

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Correspondence to Nicholas H. Williams or Christopher A. Hunter.

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The authors declare no competing financial interests.

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Langton, M., Keymeulen, F., Ciaccia, M. et al. Controlled membrane translocation provides a mechanism for signal transduction and amplification. Nature Chem 9, 426–430 (2017). https://doi.org/10.1038/nchem.2678

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