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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/218992
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/218992 |
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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 Técnicas2025-09-29T09:54:25Zoai: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:34982025-09-29 09:54:25.311CONICET 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 |
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MDPI |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |