Molecular dynamics simulation study of the effect of halothane on mixed DPPC/DPPE phospholipid membranes

  • Jorge Alfonso Arvayo-Zatarain
  • Fernando Favela-Rosales
  • Claudio Contreras-Aburto
  • Efrain Urrutia-Bañuelos
  • Amir Maldonado
Original Paper


We report results of a molecular dynamics simulation study of the effect of one general anesthetic, halothane, on some properties of mixed DPPC/DPPE phospholipid membranes. This is a suitable model for the study of simple, two-phospholipid membrane systems. From the simulation runs, we determined several membrane properties for five different molecular proportions of DPPC/DPPE. The effect of halothane on the studied membrane properties (area per lipid molecule, density of membrane, order parameter, etc.) was rather small. The distribution of halothane is not uniform through the bilayer thickness. Instead, there is a maximum of anesthetic concentration around 1.2 nm from the center of the membrane. The anesthetic molecule is located close to the phospholipid headgroups. The position of the halothane density maximum depends slightly on the DPPC/DPPE molar proportion. Snapshots taken over the plane of the membrane, as well as calculated two-dimensional radial distribution functions show that the anesthetic has no preference for either phospholipid (DPPC or DPPE). Our results indicate that this anesthetic molecule has only small effects on DPPC/DPPE mixed membranes. In addition, halothane displays no preferential location around DPPC or DPPE. This is probably due to the hydrophobic nature of halothane and to the fact that the chosen phospholipids have the same hydrophobic tails.


Phospholipid membranes Molecular dynamics Anesthetic Halotane 



This work was partially funded by Consejo Nacional de Ciencia y Tecnología–México (Conacyt; grant 256753). J.A.A.-Z. acknowledges Conacyt for a graduate fellowship. F.F.R. acknowledges Instituto Tecnológico Superior Zacatecas Occidente (ITSZO) and Dirección General de Asuntos del Personal Académico (DGAPA) Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) IG100416 for financial support and Clúster Híbrido de Supercómputo Xiuhcoatl-CINVESTAV (Centro de Investigación y de Estudios Avanzados) and Miztli-Dirección de Cómputo y de Tecnologías de Información y Comunicación (DGTIC)-Universidad Nacional Autónoma de México (UNAM) (Project LANCAD-UNAM-DGTIC-028) facilities for computing-time allocation. C.C.A. acknowledges the Mexican Ministry of Education for support through the PRODEP program "Apoyo a la Incorporación de Nuevo PTC". We thank ACARUS-Unison for access to computing facilities.

Supplementary material

894_2018_3890_MOESM1_ESM.docx (1.2 mb)
Fig. S1a–e Snapshots of DPPC:DPPE membranes without anesthetic. Phospholipid molar proportions: a 100:0, b 0:100, c 50:50, d 75:25, e 25:75. Molecules: Red DPPC, green DPPE, blue water. (DOCX 1234 kb)
894_2018_3890_MOESM2_ESM.docx (473 kb)
Fig. S2 Total density (solid line) and halothane density (dot-dashed line) for a 0:100 DPPC:DPPE membrane. The halothane density curve has been shifted in order to match the edges of both graphs. (DOCX 473 kb)
894_2018_3890_MOESM3_ESM.docx (23 kb)
Fig. S3 Total density (solid line) and halothane density (dot-dashed line) for a 25:75 DPPC:DPPE membrane. The halothane density curve has been shifted in order to match the edges of both graphs. (DOCX 23 kb)
894_2018_3890_MOESM4_ESM.docx (23 kb)
Fig. S4 Total density (solid line) and halothane density (dot-dashed line) for a 75:25 DPPC:DPPE membrane. The halothane density curve has been shifted in order to match the edges of both graphs. (DOCX 23 kb)
894_2018_3890_MOESM5_ESM.docx (23 kb)
Fig. S5 Total density (solid line) and halothane density (dot-dashed line) for a 100:0 DPPC:DPPE membrane. The halothane density curve has been shifted in order to match the edges of both graphs. (DOCX 23 kb)
894_2018_3890_MOESM6_ESM.docx (23 kb)
Fig. S6a,b Topviews of snapshots for DPPC:DPPE membranes with halothane. Phospholipid molar proportions: a 100:0, b 0:100. Molecules: Red DPPC, green DPPE, black halothane. (DOCX 23 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Posgrado en MaterialesUniversidad de SonoraHermosilloMexico
  2. 2.Departamento de InvestigaciónInstituto Tecnológico Superior Zacatecas OccidenteSombrereteMexico
  3. 3.Facultad de Ciencias en Física y MatemáticasUniversidad Autónoma de ChiapasTuxtla GutiérrezMexico
  4. 4.Departamento de Investigación en FísicaUniversidad de SonoraHermosilloMexico
  5. 5.Departamento de FísicaUniversidad de SonoraHermosilloMexico

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