The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers

Autores
Felsztyna, Iván; Sánchez Borzone, Mariela E.; Miguel, Virginia; Garcia, Daniel Asmed
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.
Fil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Sánchez Borzone, Mariela E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Materia
FIPRONIL
GABAERGIC INSECTICIDES
LANGMUIR MONOLAYERS
MOLECULAR DYNAMICS SIMULATIONS
DRUG-MEMBRANE INTERACTION
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:11336/119915
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/119915
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayersFelsztyna, IvánSánchez Borzone, Mariela E.Miguel, VirginiaGarcia, Daniel AsmedFIPRONILGABAERGIC INSECTICIDESLANGMUIR MONOLAYERSMOLECULAR DYNAMICS SIMULATIONSDRUG-MEMBRANE INTERACTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.Fil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Sánchez Borzone, Mariela E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaElsevier Science2020-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/119915Felsztyna, Iván; Sánchez Borzone, Mariela E.; Miguel, Virginia; Garcia, Daniel Asmed; The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1862; 10; 1-10-2020; 1-12; 1833780005-2736CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0005273620302200info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2020.183378info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:04:33Zoai:ri.conicet.gov.ar:11336/119915instacron: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 10:04:33.467CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
title The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
spellingShingle The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
Felsztyna, Iván
FIPRONIL
GABAERGIC INSECTICIDES
LANGMUIR MONOLAYERS
MOLECULAR DYNAMICS SIMULATIONS
DRUG-MEMBRANE INTERACTION
title_short The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
title_full The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
title_fullStr The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
title_full_unstemmed The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
title_sort The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers
dc.creator.none.fl_str_mv Felsztyna, Iván
Sánchez Borzone, Mariela E.
Miguel, Virginia
Garcia, Daniel Asmed
author Felsztyna, Iván
author_facet Felsztyna, Iván
Sánchez Borzone, Mariela E.
Miguel, Virginia
Garcia, Daniel Asmed
author_role author
author2 Sánchez Borzone, Mariela E.
Miguel, Virginia
Garcia, Daniel Asmed
author2_role author
author
author
dc.subject.none.fl_str_mv FIPRONIL
GABAERGIC INSECTICIDES
LANGMUIR MONOLAYERS
MOLECULAR DYNAMICS SIMULATIONS
DRUG-MEMBRANE INTERACTION
topic FIPRONIL
GABAERGIC INSECTICIDES
LANGMUIR MONOLAYERS
MOLECULAR DYNAMICS SIMULATIONS
DRUG-MEMBRANE INTERACTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.
Fil: Felsztyna, Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Sánchez Borzone, Mariela E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Miguel, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
description Fipronil is a widely used commercial insecticide whose action mechanism consists in blocking the influx of chloride ions through the γ-aminobutyric acid type A receptor (GABAA-R), an integral membrane protein. The present study investigates the interaction of fipronil with phospholipid Langmuir monolayers, in order to characterize the effects that its partition could exert on the physical properties of these model membranes. A combined experimental and molecular dynamics (MD) simulations approach was performed. MD simulations were conducted in such a way that they resemble an experimental compression isotherm of DPPC in the presence of fipronil in the aqueous subphase. Both the experimental and the simulated compression isotherm showed that the partition of fipronil between DPPC molecules induces an expansion of the monolayer. Experimental results also showed that fipronil can penetrate lipid monolayers even in condensed packing states. MD simulations showed that fipronil induces an ordering effect in the acyl chains of DPPC in the liquid-condensed phase. In addition, the simulations indicate that fipronil orients parallel to the plane of the monolayer and that it establishes hydrogen bonds with the glycerol region of DPPC. Free energy profiles of the partition of fipronil into the monolayers, obtained by means of umbrella sampling, indicated that its penetration is thermodynamically favorable, being the interphase between the glycerol region and the acyl chains of DPPC its most favorable location. Our results suggest that fipronil could modulate the supramolecular organization of biological membranes surrounding GABAA-R, contributing, at least in part, to its action mechanism.
publishDate 2020
dc.date.none.fl_str_mv 2020-10-01
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/11336/119915
Felsztyna, Iván; Sánchez Borzone, Mariela E.; Miguel, Virginia; Garcia, Daniel Asmed; The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1862; 10; 1-10-2020; 1-12; 183378
0005-2736
CONICET Digital
CONICET
url http://hdl.handle.net/11336/119915
identifier_str_mv Felsztyna, Iván; Sánchez Borzone, Mariela E.; Miguel, Virginia; Garcia, Daniel Asmed; The insecticide fipronil affects the physical properties of model membranes: A combined experimental and molecular dynamics simulations study in Langmuir monolayers; Elsevier Science; Biochimica et Biophysica Acta - Biomembranes; 1862; 10; 1-10-2020; 1-12; 183378
0005-2736
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0005273620302200
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbamem.2020.183378
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 Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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