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Reversible Photocontrolled Nanopore Assembly

Mutter, N. L., Volarić, J., Szymanski, W., Feringa, B. L. & Maglia, G., 11-Sep-2019, In : Journal of the American Chemical Society. 141, 36, p. 14356-14363 8 p.

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DOI

Self-assembly is a fundamental feature of biological systems, and control of such processes offers fascinating opportunities to regulate function. Fragaceatoxin C (FraC) is a toxin that upon binding to the surface of sphingomyelin-rich cells undergoes a structural metamorphosis, leading to the assembly of nanopores at the cell membrane and causing cell death. In this study we attached photoswitchable azobenzene pendants to various locations near the sphingomyelin binding pocket of FraC with the aim of remote controlling the nanopore assembly using light. We found several constructs in which the affinity of the toxin for biological membranes could be activated or deactivated by irradiation, thus enabling reversible photocontrol of pore formation. Notably, one construct was completely inactive in the thermally adapted state; it however induced full lysis of cultured cancer cells upon light irradiation. Selective irradiation also allowed isolation of individual nanopores in artificial lipid membranes. Photocontrolled FraC might find applications in photopharmacology for cancer therapeutics and has potential to be used for the fabrication of nanopore arrays in nanopore sensing devices, where the reconstitution, with high spatiotemporal precision, of single nanopores must be controlled.

Original languageEnglish
Pages (from-to)14356-14363
Number of pages8
JournalJournal of the American Chemical Society
Volume141
Issue number36
Publication statusPublished - 11-Sep-2019

    Keywords

  • PORE-FORMING TOXIN, OPTICAL CONTROL, ION CHANNELS, AZOBENZENE PHOTOSWITCHES, PHOTOCHEMICAL CONTROL, GLUTAMATE-RECEPTOR, EQUINATOXIN-II, SEA-ANEMONE, PROTEIN, PEPTIDE

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