Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models

Zsófia Borbála Rózsa, Lukács József Németh, Balázs Jójárt, Károly Nehéz, B. Viskolcz, Milán Szőri

Research output: Contribution to journalArticle

Abstract

1,4-Dioxane is a cytotoxic B2-type human carcinogen, a serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed of dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear and polluted membranes were compared by membrane parameters such as area per lipid (APL), volume per lipid (VPL), compressibility modulus, membrane thickness, and orderliness of lipid tails. While neat systems significantly differ from each other, the presence of the pollutant has the same effect on both types of lipid membranes. High density of dioxane appears in the vicinity of ester groups, which pushes away lipid headgroups from each other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of lipid tails, membrane thickness, and compressibility modulus decrease. Orientational preferences of water and dioxane molecules were also investigated and different membrane regions have been specified according to the stance of water molecules. Free-energy profile for 1,4-dioxane penetration mechanism into DPPC membranes was carried out using metadynamics for two different concentrations of the pollutant (c1 = 7.51 g/dm3, c2 = 75.10 g/dm3), which showed that the higher the concentration is, the lower the free energy of penetration gets. Only a small free-energy barrier was found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the middle of the bilayer. The penetration mechanism has been described in detail based on the orientational preference of 1,4-dioxane molecules and the free-energy profiles.

Original languageEnglish
Pages (from-to)7869-7884
Number of pages16
JournalThe journal of physical chemistry. B
Volume123
Issue number37
DOIs
Publication statusPublished - Sep 19 2019

Fingerprint

Lipids
lipids
Molecular dynamics
molecular dynamics
membranes
Membranes
Free energy
free energy
1,2-Dipalmitoylphosphatidylcholine
contaminants
penetration
Compressibility
Molecules
compressibility
Water Pollutants
Water
Carcinogens
carcinogens
water
1,4-dioxane

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models. / Rózsa, Zsófia Borbála; Németh, Lukács József; Jójárt, Balázs; Nehéz, Károly; Viskolcz, B.; Szőri, Milán.

In: The journal of physical chemistry. B, Vol. 123, No. 37, 19.09.2019, p. 7869-7884.

Research output: Contribution to journalArticle

Rózsa, Zsófia Borbála ; Németh, Lukács József ; Jójárt, Balázs ; Nehéz, Károly ; Viskolcz, B. ; Szőri, Milán. / Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models. In: The journal of physical chemistry. B. 2019 ; Vol. 123, No. 37. pp. 7869-7884.
@article{33a5f56d3f73446ab1c4b03fa0a92c8c,
title = "Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models",
abstract = "1,4-Dioxane is a cytotoxic B2-type human carcinogen, a serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed of dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear and polluted membranes were compared by membrane parameters such as area per lipid (APL), volume per lipid (VPL), compressibility modulus, membrane thickness, and orderliness of lipid tails. While neat systems significantly differ from each other, the presence of the pollutant has the same effect on both types of lipid membranes. High density of dioxane appears in the vicinity of ester groups, which pushes away lipid headgroups from each other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of lipid tails, membrane thickness, and compressibility modulus decrease. Orientational preferences of water and dioxane molecules were also investigated and different membrane regions have been specified according to the stance of water molecules. Free-energy profile for 1,4-dioxane penetration mechanism into DPPC membranes was carried out using metadynamics for two different concentrations of the pollutant (c1 = 7.51 g/dm3, c2 = 75.10 g/dm3), which showed that the higher the concentration is, the lower the free energy of penetration gets. Only a small free-energy barrier was found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the middle of the bilayer. The penetration mechanism has been described in detail based on the orientational preference of 1,4-dioxane molecules and the free-energy profiles.",
author = "R{\'o}zsa, {Zs{\'o}fia Borb{\'a}la} and N{\'e}meth, {Luk{\'a}cs J{\'o}zsef} and Bal{\'a}zs J{\'o}j{\'a}rt and K{\'a}roly Neh{\'e}z and B. Viskolcz and Mil{\'a}n Szőri",
year = "2019",
month = "9",
day = "19",
doi = "10.1021/acs.jpcb.9b04313",
language = "English",
volume = "123",
pages = "7869--7884",
journal = "The journal of physical chemistry. B",
issn = "1520-6106",
number = "37",

}

TY - JOUR

T1 - Molecular Dynamics and Metadynamics Insights of 1,4-Dioxane-Induced Structural Changes of Biomembrane Models

AU - Rózsa, Zsófia Borbála

AU - Németh, Lukács József

AU - Jójárt, Balázs

AU - Nehéz, Károly

AU - Viskolcz, B.

AU - Szőri, Milán

PY - 2019/9/19

Y1 - 2019/9/19

N2 - 1,4-Dioxane is a cytotoxic B2-type human carcinogen, a serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed of dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear and polluted membranes were compared by membrane parameters such as area per lipid (APL), volume per lipid (VPL), compressibility modulus, membrane thickness, and orderliness of lipid tails. While neat systems significantly differ from each other, the presence of the pollutant has the same effect on both types of lipid membranes. High density of dioxane appears in the vicinity of ester groups, which pushes away lipid headgroups from each other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of lipid tails, membrane thickness, and compressibility modulus decrease. Orientational preferences of water and dioxane molecules were also investigated and different membrane regions have been specified according to the stance of water molecules. Free-energy profile for 1,4-dioxane penetration mechanism into DPPC membranes was carried out using metadynamics for two different concentrations of the pollutant (c1 = 7.51 g/dm3, c2 = 75.10 g/dm3), which showed that the higher the concentration is, the lower the free energy of penetration gets. Only a small free-energy barrier was found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the middle of the bilayer. The penetration mechanism has been described in detail based on the orientational preference of 1,4-dioxane molecules and the free-energy profiles.

AB - 1,4-Dioxane is a cytotoxic B2-type human carcinogen, a serious water pollutant produced solely by industrial activity. The effect of 1,4-dioxane on phospholipid membrane models composed of dipalmitoyl-phosphatidylcholine (DPPC) and its branched isomer (isodipalmitoyl-phosphatidylcholine, IPPC) was investigated using MD simulations. Clear and polluted membranes were compared by membrane parameters such as area per lipid (APL), volume per lipid (VPL), compressibility modulus, membrane thickness, and orderliness of lipid tails. While neat systems significantly differ from each other, the presence of the pollutant has the same effect on both types of lipid membranes. High density of dioxane appears in the vicinity of ester groups, which pushes away lipid headgroups from each other, leading to an overall change in lipid structure: APL and VPL grows, while the orderliness of lipid tails, membrane thickness, and compressibility modulus decrease. Orientational preferences of water and dioxane molecules were also investigated and different membrane regions have been specified according to the stance of water molecules. Free-energy profile for 1,4-dioxane penetration mechanism into DPPC membranes was carried out using metadynamics for two different concentrations of the pollutant (c1 = 7.51 g/dm3, c2 = 75.10 g/dm3), which showed that the higher the concentration is, the lower the free energy of penetration gets. Only a small free-energy barrier was found in the headgroup region and accumulation of dioxane is thermodynamically unfavored in the middle of the bilayer. The penetration mechanism has been described in detail based on the orientational preference of 1,4-dioxane molecules and the free-energy profiles.

UR - http://www.scopus.com/inward/record.url?scp=85072509233&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072509233&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.9b04313

DO - 10.1021/acs.jpcb.9b04313

M3 - Article

C2 - 31452375

AN - SCOPUS:85072509233

VL - 123

SP - 7869

EP - 7884

JO - The journal of physical chemistry. B

JF - The journal of physical chemistry. B

SN - 1520-6106

IS - 37

ER -