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Reversible Photocontrolled Nanopore Assembly

[Image: see text] 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, le...

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Autores principales: Mutter, Natalie L., Volarić, Jana, Szymanski, Wiktor, Feringa, Ben L., Maglia, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743218/
https://www.ncbi.nlm.nih.gov/pubmed/31469268
http://dx.doi.org/10.1021/jacs.9b06998
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author Mutter, Natalie L.
Volarić, Jana
Szymanski, Wiktor
Feringa, Ben L.
Maglia, Giovanni
author_facet Mutter, Natalie L.
Volarić, Jana
Szymanski, Wiktor
Feringa, Ben L.
Maglia, Giovanni
author_sort Mutter, Natalie L.
collection PubMed
description [Image: see text] 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.
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spelling pubmed-67432182019-09-16 Reversible Photocontrolled Nanopore Assembly Mutter, Natalie L. Volarić, Jana Szymanski, Wiktor Feringa, Ben L. Maglia, Giovanni J Am Chem Soc [Image: see text] 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. American Chemical Society 2019-08-30 2019-09-11 /pmc/articles/PMC6743218/ /pubmed/31469268 http://dx.doi.org/10.1021/jacs.9b06998 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Mutter, Natalie L.
Volarić, Jana
Szymanski, Wiktor
Feringa, Ben L.
Maglia, Giovanni
Reversible Photocontrolled Nanopore Assembly
title Reversible Photocontrolled Nanopore Assembly
title_full Reversible Photocontrolled Nanopore Assembly
title_fullStr Reversible Photocontrolled Nanopore Assembly
title_full_unstemmed Reversible Photocontrolled Nanopore Assembly
title_short Reversible Photocontrolled Nanopore Assembly
title_sort reversible photocontrolled nanopore assembly
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743218/
https://www.ncbi.nlm.nih.gov/pubmed/31469268
http://dx.doi.org/10.1021/jacs.9b06998
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