The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I

Autores
Pedrera, Lohans; Ros, Uris; Fanani, Maria Laura; Lanio, María E.; Epand, Richard M.; García-Sáez, Ana J.; Álvarez, Carlos
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Actinoporins have emerged as archetypal α-pore-forming toxins (PFTs) that promote the formation of pores in membranes upon oligomerization and insertion of an α-helix pore-forming domain in the bilayer. These proteins have been used as active components of immunotoxins, therefore, understanding their lytic mechanism is crucial for developing this and other applications. However, the mechanism of how the biophysical properties of the membrane modulate the properties of pores generated by actinoporins remains unclear. Here we studied the effect of membrane fluidity on the permeabilizing activity of sticholysin I (St I), a toxin that belongs to the actinoporins family of α-PFTs. To modulate membrane fluidity we used vesicles made of an equimolar mixture of phosphatidylcholine (PC) and egg sphingomyelin (eggSM), in which PC contained fatty acids of different acyl chain lengths and degrees of unsaturation. Our detailed single-vesicle analysis revealed that when membrane fluidity is high, most of the vesicles are partially permeabilized in a graded manner. In contrast, more rigid membranes can be either completely permeabilized or not, indicating an all-or-none mechanism. Altogether, our results reveal that St I pores can be heterogeneous in size and stability, and that these properties depend on the fluid state of the lipid bilayer. We propose that membrane fluidity at different regions of cellular membranes is a key factor to modulate the activity of the actinoporins, which has implications for the design of different therapeutic strategies based on their lytic action.
Fil: Pedrera, Lohans. Universidad de La Habana; Cuba. Universitat zu Köln; Alemania
Fil: Ros, Uris. Universidad de La Habana; Cuba. Universitat zu Köln; Alemania
Fil: Fanani, Maria Laura. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Lanio, María E.. Universidad de La Habana; Cuba
Fil: Epand, Richard M.. Mcmaster University, Faculty Of Health Sciences; Canadá
Fil: García-Sáez, Ana J.. Universitat zu Köln; Alemania
Fil: Álvarez, Carlos. Universidad de La Habana; Cuba
Materia
ACTINOPORINS
LIPID PHASE-COEXISTENCE
MEMBRANE FLUIDITY
MEMBRANE PERMEABILIZATION
PORE-FORMING TOXINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/218992
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/218992
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin IPedrera, LohansRos, UrisFanani, Maria LauraLanio, María E.Epand, Richard M.García-Sáez, Ana J.Álvarez, CarlosACTINOPORINSLIPID PHASE-COEXISTENCEMEMBRANE FLUIDITYMEMBRANE PERMEABILIZATIONPORE-FORMING TOXINShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Actinoporins have emerged as archetypal α-pore-forming toxins (PFTs) that promote the formation of pores in membranes upon oligomerization and insertion of an α-helix pore-forming domain in the bilayer. These proteins have been used as active components of immunotoxins, therefore, understanding their lytic mechanism is crucial for developing this and other applications. However, the mechanism of how the biophysical properties of the membrane modulate the properties of pores generated by actinoporins remains unclear. Here we studied the effect of membrane fluidity on the permeabilizing activity of sticholysin I (St I), a toxin that belongs to the actinoporins family of α-PFTs. To modulate membrane fluidity we used vesicles made of an equimolar mixture of phosphatidylcholine (PC) and egg sphingomyelin (eggSM), in which PC contained fatty acids of different acyl chain lengths and degrees of unsaturation. Our detailed single-vesicle analysis revealed that when membrane fluidity is high, most of the vesicles are partially permeabilized in a graded manner. In contrast, more rigid membranes can be either completely permeabilized or not, indicating an all-or-none mechanism. Altogether, our results reveal that St I pores can be heterogeneous in size and stability, and that these properties depend on the fluid state of the lipid bilayer. We propose that membrane fluidity at different regions of cellular membranes is a key factor to modulate the activity of the actinoporins, which has implications for the design of different therapeutic strategies based on their lytic action.Fil: Pedrera, Lohans. Universidad de La Habana; Cuba. Universitat zu Köln; AlemaniaFil: Ros, Uris. Universidad de La Habana; Cuba. Universitat zu Köln; AlemaniaFil: Fanani, Maria Laura. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Lanio, María E.. Universidad de La Habana; CubaFil: Epand, Richard M.. Mcmaster University, Faculty Of Health Sciences; CanadáFil: García-Sáez, Ana J.. Universitat zu Köln; AlemaniaFil: Álvarez, Carlos. Universidad de La Habana; CubaMDPI2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218992Pedrera, Lohans; Ros, Uris; Fanani, Maria Laura; Lanio, María E.; Epand, Richard M.; et al.; The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I; MDPI; Toxins; 15; 1; 1-2023; 80-992072-6651CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/toxins15010080info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/15/1/80info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:23:42Zoai:ri.conicet.gov.ar:11336/218992instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:23:42.272CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
title The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
spellingShingle The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
Pedrera, Lohans
ACTINOPORINS
LIPID PHASE-COEXISTENCE
MEMBRANE FLUIDITY
MEMBRANE PERMEABILIZATION
PORE-FORMING TOXINS
title_short The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
title_full The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
title_fullStr The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
title_full_unstemmed The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
title_sort The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I
dc.creator.none.fl_str_mv Pedrera, Lohans
Ros, Uris
Fanani, Maria Laura
Lanio, María E.
Epand, Richard M.
García-Sáez, Ana J.
Álvarez, Carlos
author Pedrera, Lohans
author_facet Pedrera, Lohans
Ros, Uris
Fanani, Maria Laura
Lanio, María E.
Epand, Richard M.
García-Sáez, Ana J.
Álvarez, Carlos
author_role author
author2 Ros, Uris
Fanani, Maria Laura
Lanio, María E.
Epand, Richard M.
García-Sáez, Ana J.
Álvarez, Carlos
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTINOPORINS
LIPID PHASE-COEXISTENCE
MEMBRANE FLUIDITY
MEMBRANE PERMEABILIZATION
PORE-FORMING TOXINS
topic ACTINOPORINS
LIPID PHASE-COEXISTENCE
MEMBRANE FLUIDITY
MEMBRANE PERMEABILIZATION
PORE-FORMING TOXINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Actinoporins have emerged as archetypal α-pore-forming toxins (PFTs) that promote the formation of pores in membranes upon oligomerization and insertion of an α-helix pore-forming domain in the bilayer. These proteins have been used as active components of immunotoxins, therefore, understanding their lytic mechanism is crucial for developing this and other applications. However, the mechanism of how the biophysical properties of the membrane modulate the properties of pores generated by actinoporins remains unclear. Here we studied the effect of membrane fluidity on the permeabilizing activity of sticholysin I (St I), a toxin that belongs to the actinoporins family of α-PFTs. To modulate membrane fluidity we used vesicles made of an equimolar mixture of phosphatidylcholine (PC) and egg sphingomyelin (eggSM), in which PC contained fatty acids of different acyl chain lengths and degrees of unsaturation. Our detailed single-vesicle analysis revealed that when membrane fluidity is high, most of the vesicles are partially permeabilized in a graded manner. In contrast, more rigid membranes can be either completely permeabilized or not, indicating an all-or-none mechanism. Altogether, our results reveal that St I pores can be heterogeneous in size and stability, and that these properties depend on the fluid state of the lipid bilayer. We propose that membrane fluidity at different regions of cellular membranes is a key factor to modulate the activity of the actinoporins, which has implications for the design of different therapeutic strategies based on their lytic action.
Fil: Pedrera, Lohans. Universidad de La Habana; Cuba. Universitat zu Köln; Alemania
Fil: Ros, Uris. Universidad de La Habana; Cuba. Universitat zu Köln; Alemania
Fil: Fanani, Maria Laura. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina
Fil: Lanio, María E.. Universidad de La Habana; Cuba
Fil: Epand, Richard M.. Mcmaster University, Faculty Of Health Sciences; Canadá
Fil: García-Sáez, Ana J.. Universitat zu Köln; Alemania
Fil: Álvarez, Carlos. Universidad de La Habana; Cuba
description Actinoporins have emerged as archetypal α-pore-forming toxins (PFTs) that promote the formation of pores in membranes upon oligomerization and insertion of an α-helix pore-forming domain in the bilayer. These proteins have been used as active components of immunotoxins, therefore, understanding their lytic mechanism is crucial for developing this and other applications. However, the mechanism of how the biophysical properties of the membrane modulate the properties of pores generated by actinoporins remains unclear. Here we studied the effect of membrane fluidity on the permeabilizing activity of sticholysin I (St I), a toxin that belongs to the actinoporins family of α-PFTs. To modulate membrane fluidity we used vesicles made of an equimolar mixture of phosphatidylcholine (PC) and egg sphingomyelin (eggSM), in which PC contained fatty acids of different acyl chain lengths and degrees of unsaturation. Our detailed single-vesicle analysis revealed that when membrane fluidity is high, most of the vesicles are partially permeabilized in a graded manner. In contrast, more rigid membranes can be either completely permeabilized or not, indicating an all-or-none mechanism. Altogether, our results reveal that St I pores can be heterogeneous in size and stability, and that these properties depend on the fluid state of the lipid bilayer. We propose that membrane fluidity at different regions of cellular membranes is a key factor to modulate the activity of the actinoporins, which has implications for the design of different therapeutic strategies based on their lytic action.
publishDate 2023
dc.date.none.fl_str_mv 2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/218992
Pedrera, Lohans; Ros, Uris; Fanani, Maria Laura; Lanio, María E.; Epand, Richard M.; et al.; The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I; MDPI; Toxins; 15; 1; 1-2023; 80-99
2072-6651
CONICET Digital
CONICET
url http://hdl.handle.net/11336/218992
identifier_str_mv Pedrera, Lohans; Ros, Uris; Fanani, Maria Laura; Lanio, María E.; Epand, Richard M.; et al.; The important role of membrane fluidity on the lytic mechanism of the α-Pore-Forming Toxin Sticholysin I; MDPI; Toxins; 15; 1; 1-2023; 80-99
2072-6651
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/toxins15010080
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6651/15/1/80
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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