In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M

Gao, Li; Meiring, Joyce C. M.; Varady, Adam; Ruider, Iris E.; Heise, Constanze; Wranik, Maximilian; Velasco, Cecilia D.; Taylor, Jennifer A.; Terni, Beatrice; Weinert, Tobias; Standfuss, Jörg; Cabernard, Clemens C.; Llobet Berenguer, Artur, 1972-; Steinmetz, Michel O.; Bausch, Andreas R.; Distel, Martin; Thorn-Seshold, Julia; Akhmanova, Anna; Thorn-Seshold, Oliver

In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M

Photoswitchable reagents arc powerful tools for high-precision studies in cell biology. When these reagents are globally administered yet locally photoactivated in two-dimensional (2D) cell cultures, they can exert micron- and millisecond-scale biological control. This gives them great potential for...

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Autores:	Gao, Li, Meiring, Joyce C. M., Varady, Adam, Ruider, Iris E., Heise, Constanze, Wranik, Maximilian, Velasco, Cecilia D., Taylor, Jennifer A., Terni, Beatrice, Weinert, Tobias, Standfuss, Jörg, Cabernard, Clemens C., Llobet Berenguer, Artur, 1972-, Steinmetz, Michel O., Bausch, Andreas R., Distel, Martin, Thorn-Seshold, Julia, Akhmanova, Anna, Thorn-Seshold, Oliver
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2022
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/186228
Acceso en línea:	https://hdl.handle.net/2445/186228
Access Level:	acceso abierto
Palabra clave:	Citosquelet Mitosi Cytoskeleton Mitosis

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spelling	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2MGao, LiMeiring, Joyce C. M.Varady, AdamRuider, Iris E.Heise, ConstanzeWranik, MaximilianVelasco, Cecilia D.Taylor, Jennifer A.Terni, BeatriceWeinert, TobiasStandfuss, JörgCabernard, Clemens C.Llobet Berenguer, Artur, 1972-Steinmetz, Michel O.Bausch, Andreas R.Distel, MartinThorn-Seshold, JuliaAkhmanova, AnnaThorn-Seshold, OliverCitosqueletMitosiCytoskeletonMitosisPhotoswitchable reagents arc powerful tools for high-precision studies in cell biology. When these reagents are globally administered yet locally photoactivated in two-dimensional (2D) cell cultures, they can exert micron- and millisecond-scale biological control. This gives them great potential for use in biologically more relevant three-dimensional (3D) models and in vivo, particularly for studying systems with inherent spatiotemporal complexity, such as the cytoskeleton. However, due to a combination of photoswitch isomerization under typical imaging conditions, metabolic liabilities, and insufficient water solubility at effective concentrations, the in vivo potential of photoswitchable reagents addressing cytosolic protein targets remains largely unrealized. Here, we optimized the potency and solubility of metabolically stable, druglike colchicinoid microtubule inhibitors based on the styrylbenzothiazole (SBT) scaffold that are nonresponsive to typical fluorescent protein imaging wavelengths and so enable multichannel imaging studies. We applied these reagents both to 3D organoids and tissue explants and to classic model organisms (zebrafish, clawed frog) in one- and two-protein imaging experiments, in which spatiotemporally localized illuminations allowed them to photocontrol microtubule dynamics, network architecture, and microtubule-dependent processes in vivo with cellular precision and second-level resolution. These nanomolar, in vivo capable photoswitchable reagents should open up new dimensions for high-precision cytoskeleton research in cargo transport, cell motility, cell division, and development. More broadly, their design can also inspire similarly capable optical reagents for a range of cytosolic protein targets, thus bringing in vivo photopharmacology one step doser to general realization.American Chemical Society (ACS)2022202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/186228Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1021/jacs.2c01020Journal of the American Chemical Society, 2022, vol. 144, num. 12, p. 5614-5628https://doi.org/10.1021/jacs.2c01020cc by-nc-nd (c) Gao, Li et al, 2022http://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1862282026-05-29T05:05:01Z
dc.title.none.fl_str_mv	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
title	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
spellingShingle	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M Gao, Li Citosquelet Mitosi Cytoskeleton Mitosis
title_short	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
title_full	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
title_fullStr	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
title_full_unstemmed	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
title_sort	In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M
dc.creator.none.fl_str_mv	Gao, Li Meiring, Joyce C. M. Varady, Adam Ruider, Iris E. Heise, Constanze Wranik, Maximilian Velasco, Cecilia D. Taylor, Jennifer A. Terni, Beatrice Weinert, Tobias Standfuss, Jörg Cabernard, Clemens C. Llobet Berenguer, Artur, 1972- Steinmetz, Michel O. Bausch, Andreas R. Distel, Martin Thorn-Seshold, Julia Akhmanova, Anna Thorn-Seshold, Oliver
author	Gao, Li
author_facet	Gao, Li Meiring, Joyce C. M. Varady, Adam Ruider, Iris E. Heise, Constanze Wranik, Maximilian Velasco, Cecilia D. Taylor, Jennifer A. Terni, Beatrice Weinert, Tobias Standfuss, Jörg Cabernard, Clemens C. Llobet Berenguer, Artur, 1972- Steinmetz, Michel O. Bausch, Andreas R. Distel, Martin Thorn-Seshold, Julia Akhmanova, Anna Thorn-Seshold, Oliver
author_role	author
author2	Meiring, Joyce C. M. Varady, Adam Ruider, Iris E. Heise, Constanze Wranik, Maximilian Velasco, Cecilia D. Taylor, Jennifer A. Terni, Beatrice Weinert, Tobias Standfuss, Jörg Cabernard, Clemens C. Llobet Berenguer, Artur, 1972- Steinmetz, Michel O. Bausch, Andreas R. Distel, Martin Thorn-Seshold, Julia Akhmanova, Anna Thorn-Seshold, Oliver
author2_role	author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Citosquelet Mitosi Cytoskeleton Mitosis
topic	Citosquelet Mitosi Cytoskeleton Mitosis
description	Photoswitchable reagents arc powerful tools for high-precision studies in cell biology. When these reagents are globally administered yet locally photoactivated in two-dimensional (2D) cell cultures, they can exert micron- and millisecond-scale biological control. This gives them great potential for use in biologically more relevant three-dimensional (3D) models and in vivo, particularly for studying systems with inherent spatiotemporal complexity, such as the cytoskeleton. However, due to a combination of photoswitch isomerization under typical imaging conditions, metabolic liabilities, and insufficient water solubility at effective concentrations, the in vivo potential of photoswitchable reagents addressing cytosolic protein targets remains largely unrealized. Here, we optimized the potency and solubility of metabolically stable, druglike colchicinoid microtubule inhibitors based on the styrylbenzothiazole (SBT) scaffold that are nonresponsive to typical fluorescent protein imaging wavelengths and so enable multichannel imaging studies. We applied these reagents both to 3D organoids and tissue explants and to classic model organisms (zebrafish, clawed frog) in one- and two-protein imaging experiments, in which spatiotemporally localized illuminations allowed them to photocontrol microtubule dynamics, network architecture, and microtubule-dependent processes in vivo with cellular precision and second-level resolution. These nanomolar, in vivo capable photoswitchable reagents should open up new dimensions for high-precision cytoskeleton research in cargo transport, cell motility, cell division, and development. More broadly, their design can also inspire similarly capable optical reagents for a range of cytosolic protein targets, thus bringing in vivo photopharmacology one step doser to general realization.
publishDate	2022
dc.date.none.fl_str_mv	2022 2022 2022 2022
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/186228
url	https://hdl.handle.net/2445/186228
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1021/jacs.2c01020 Journal of the American Chemical Society, 2022, vol. 144, num. 12, p. 5614-5628 https://doi.org/10.1021/jacs.2c01020
dc.rights.none.fl_str_mv	cc by-nc-nd (c) Gao, Li et al, 2022 http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by-nc-nd (c) Gao, Li et al, 2022 http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	15 p. application/pdf
dc.publisher.none.fl_str_mv	American Chemical Society (ACS)
publisher.none.fl_str_mv	American Chemical Society (ACS)
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15.198674

In Vivo Photocontrol of Microtubule Dynamics and Integrity, Migration and Mitosis, by the Potent GFP-Imaging-Compatible Photoswitchable Reagents SBTubA4P and SBTub2M

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