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

Autor: Felsztyna I; Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales, Departamento de Química, Cátedra de Química Biológica, Córdoba, Argentina; Instituto de Investigaciones Biológicas y Tecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Sánchez-Borzone ME; Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales, Departamento de Química, Cátedra de Química Biológica, Córdoba, Argentina; Instituto de Investigaciones Biológicas y Tecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Córdoba, Argentina., Miguel V; Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales, Departamento de Química, Cátedra de Química Biológica, Córdoba, Argentina; Instituto de Investigaciones Biológicas y Tecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: vmiguel@conicet.gov.ar., García DA; Universidad Nacional de Córdoba, Facultad de Ciencias Exactas, Físicas y Naturales, Departamento de Química, Cátedra de Química Biológica, Córdoba, Argentina; Instituto de Investigaciones Biológicas y Tecnológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: dagarcia@unc.edu.ar.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Biomembranes [Biochim Biophys Acta Biomembr] 2020 Oct 01; Vol. 1862 (10), pp. 183378. Date of Electronic Publication: 2020 May 25.
DOI: 10.1016/j.bbamem.2020.183378
Abstrakt: 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 (GABA A -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 GABA A -R, contributing, at least in part, to its action mechanism.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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