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.

Fipronil是一种广泛使用的商业杀虫剂，其作用机理在于通过A型γ-氨基丁酸受体（GABA _A）阻止氯离子的流入。-R），必不可少的膜蛋白。本研究调查了氟虫腈与磷脂Langmuir单层的相互作用，以表征其分配可能对这些模型膜的物理性质产生的影响。进行了组合的实验和分子动力学（MD）模拟方法。MD模拟以类似于水相亚相中存在氟虫腈的DPPC实验压缩等温线的方式进行。实验和模拟的压缩等温线均表明，氟虫腈在DPPC分子之间的分配诱导了单层的膨胀。实验结果还表明，即使在浓缩的填充状态下，氟虫腈仍可以穿透脂质单层。MD模拟显示，氟虫腈在液相中诱导DPPC的酰基链中的有序作用。此外，模拟表明氟虫腈的取向平行于单分子层的平面，并与DPPC的甘油区域建立氢键。通过伞状取样获得的氟虫腈分隔成单层的自由能分布图表明，氟虫腈的渗透在热力学上是有利的，是甘油区域和DPPC酰基链之间的界面，是其最有利的位置。我们的研究结果表明，氟虫腈可以调节GABA周围生物膜的超分子组织 模拟表明，氟虫腈的取向平行于单分子层的平面，并与DPPC的甘油区域建立氢键。通过伞状取样获得的氟虫腈分隔成单层的自由能分布图表明，氟虫腈的渗透在热力学上是有利的，是甘油区域和DPPC酰基链之间的界面，是其最有利的位置。我们的结果表明，氟虫腈可以调节GABA周围生物膜的超分子组织 模拟表明，氟虫腈的取向平行于单分子层的平面，并与DPPC的甘油区域建立氢键。通过伞状取样获得的氟虫腈分隔成单层的自由能分布图表明，氟虫腈的渗透在热力学上是有利的，是甘油区域和DPPC酰基链之间的界面，是其最有利的位置。我们的结果表明，氟虫腈可以调节GABA周围生物膜的超分子组织 是甘油区域和DPPC酰基链之间的最有利位置。我们的结果表明，氟虫腈可以调节GABA周围生物膜的超分子组织 是甘油区域和DPPC酰基链之间的最有利位置。我们的结果表明，氟虫腈可以调节GABA周围生物膜的超分子组织_甲-R，贡献，至少部分，其作用机制。