Molecular dynamics simulations in the NPT ensemble have been carried out to investigate the effect of two room temperature ionic liquids (RTILs), on stacks of phospholipid bilayers in water. We consider RTIL compounds consisting of chloride ([bmim][Cl]) and hexafluorophosphate ([bmim][PF6]) salts of the 1-buthyl-3-methylimidazolium ([bmim]+) cation, while the phospholipid bilayer is made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our investigations focus on structural and dynamical properties of phospholipid and water molecules that could be probed by inelastic and quasi-elastic neutron scattering measurements. The results confirm the fast incorporation of [bmim]+ into the lipid phase already observed in previous simulations, driven by the Coulomb attraction of the cation for the most electronegative oxygens in the POPC head group and by sizeable dispersion forces binding the neutral hydrocarbon tails of [bmim]+ and of POPC. The [bmim]+ absorption into the bilayer favours the penetration of water into POPC, causes a slight but systematic thinning of the bilayer, and further stabilises hydrogen bonds at the lipid/water interface that already in pure samples (no RTIL) display a lifetime much longer than in bulk water. On the other hand, the effect of RTILs on the diffusion constant of POPC (DPOPC) does not reveal a clearly identifiable trend, since DPOPC increases upon addition of [bmim][Cl] and decreases in the [bmim][PF6] case. Moreover, because of screening, the electrostatic signature of each bilayer is only moderately affected by the addition of RTIL ions in solution. The analysis of long wavelength fluctuations of the bilayers shows that RTIL sorption causes a general decrease of the lipid/water interfacial tension and bending rigidity, pointing to the destabilizing effect of RTILs on lipid bilayers.

2.
J. M.
Berg
,
J. L.
Tymoczko
, and
L.
Stryer
,
Biochemistry
, 7th ed. (
W.H. Freeman
,
New York
,
2012
).
3.
H.
Khesbak
,
O.
Savchuk
,
S.
Tsushima
, and
K.
Fahmy
,
J. Am. Chem. Soc.
133
,
5834
(
2011
).
5.
N. H.
Tattrie
,
J. R.
Bennett
, and
R.
Cyr
,
Can. J. Biochem.
46
,
819
(
1968
).
6.
N.
Kučerka
,
S.
Tristram-Nagle
, and
J. F.
Nagle
,
J. Membr. Biol.
208
,
193
(
2005
).
7.
J. F.
Nagle
and
S.
Tristram-Nagle
,
Biochim. Biophys. Acta
1469
,
159
(
2000
).
8.
S.
Leekumjorn
and
A. K.
Sum
,
J. Phys. Chem. B
111
,
6026
(
2007
);
[PubMed]
M.
Ceccarelli
and
M.
Marchi
,
Biochimie
80
,
415
(
1998
);
[PubMed]
A. W.
Mauk
,
E. L.
Chaikof
, and
P. J.
Ludovice
,
Langmuir
14
,
5255
(
1998
);
H.
Heller
,
M.
Schaefer
, and
K.
Schulten
,
J. Phys. Chem.
97
,
8343
(
1993
).
9.
T. D.
Lazzara
,
A.
Janshoff
, and
C.
Steinem
, in
Handbook of Nanomaterials Properties
, edited by
B.
Bhushan
,
D.
Luo
,
S. R.
Schricker
,
W.
Sigmund
, and
S.
Zauscher
(
Springer
,
Berlin
,
2014
).
10.
M. L.
Berkowitz
and
R.
Vácha
,
Acc. Chem. Res.
45
,
74
(
2012
).
11.
R.
Zimmermann
,
D.
Küttner
,
L.
Renner
,
M.
Kaufmann
, and
C.
Werner
,
J. Phys. Chem. A
116
,
6519
(
2012
).
12.
R. A.
Böckmann
,
A.
Hac
,
T.
Heimburg
, and
H.
Grubmüller
,
Biophys. J.
85
,
1647
(
2003
).
13.
S. A.
Tatulian
, in
Phospholipids Handbook
, edited by
G.
Cevc
(
Marcel Dekker
,
New York
,
1993
), pp.
511
-
552
;
P. T.
Vernier
,
M. J.
Ziegler
, and
R.
Dimova
,
Langmuir
25
,
1020
(
2009
).
[PubMed]
14.
Ionic Liquids: From Knowledge to Applications
,
ACS Symposium Series
Vol.
1030
, edited by
N. V.
Plechkova
,
R. D.
Rogers
, and
K. R.
Seddon
(
American Chemical Society
,
Washington, DC
,
2009
).
15.
M.
Petkovic
,
K. R.
Seddon
,
L. P. N.
Rebelo
, and
C. S.
Pereira
,
Chem. Soc. Rev.
40
,
1383
(
2011
);
[PubMed]
J.
Ranke
,
A.
Müller
,
U.
Bottin-Weber
,
F.
Stock
,
S.
Stolte
,
J.
Arning
,
R.
Störmann
, and
B.
Jastorff
,
Ecotoxicol. Environ. Saf.
67
,
430
(
2007
);
[PubMed]
D. J.
Couling
,
R. J.
Bernot
,
K. M.
Docherty
,
J. K.
Dixon
, and
E. J.
Maginn
,
Green Chem.
8
,
82
(
2006
).
16.
B. K.
Paul
,
A.
Ganguly
, and
N.
Guchhait
,
J. Photochem. Photobiol., B
133
,
99
(
2014
);
[PubMed]
V. F.
Curto
,
S.
Scheuermann
,
R. M.
Owens
,
R.
Vijayaraghavan
,
D. R.
MacFarlane
,
F.
Benito-Lopez
, and
D.
Diamond
,
Phys. Chem. Chem. Phys.
16
,
1841
(
2014
);
[PubMed]
N.
Byrne
and
C. A.
Angell
,
Chem. Commun.
2009
,
1046
.
17.
G.
Portella
,
M. W.
Germann
,
N. V.
Hud
, and
M.
Orozco
,
J. Am. Chem. Soc.
136
,
3075
(
2014
);
[PubMed]
M.
Nakano
,
H.
Tateishi-Karimata
,
S.
Tanaka
, and
N.
Sugimoto
,
J. Phys. Chem. B
118
,
379
(
2014
);
[PubMed]
A.
Chandran
,
D.
Ghoshdastidar
, and
S.
Senapati
,
J. Am. Chem. Soc.
134
,
20330
(
2012
);
[PubMed]
R.
Vijayaraghavan
,
A.
Izgorodin
,
V.
Ganesh
,
M.
Surianarayanan
, and
D. R.
MacFarlane
,
Angew. Chem., Int. Ed.
49
,
1631
(
2010
).
18.
S.
Jeong
,
S. H.
Ha
,
S.-H.
Han
,
M.-C.
Lim
,
S. M.
Kim
,
Y.-R.
Kim
,
Y.-M.
Koo
,
J. S.
So
, and
T.-J.
Jeon
,
Soft Matter
8
,
5501
(
2012
).
19.
K. O.
Evans
,
Colloids Surf., A
274
,
11
(
2006
).
20.
K. O.
Evans
,
J. Phys. Chem. B
112
,
8558
(
2008
).
21.
K. O.
Evans
,
Int. J. Mol. Sci.
9
,
498
(
2008
).
22.
A.
Benedetto
,
F.
Heinrich
,
M. A.
Gonzalez
,
G.
Fragneto
,
E.
Watkins
, and
P.
Ballone
,
J. Phys. Chem. B
118
,
12192
(
2014
).
23.
M.
Galluzzi
,
S.
Zhang
,
S.
Mohamadi
,
A.
Vakurov
,
A.
Podestà
, and
A.
Nelson
,
Langmuir
29
,
6573
(
2013
).
24.
S. R. T.
Cromie
,
M. G.
Del Pópolo
, and
P.
Ballone
,
J. Phys. Chem.
113
,
11642
(
2009
).
25.
R. J.
Bingham
and
P.
Ballone
,
J. Phys. Chem. B
116
,
11205
(
2012
).
26.
G. S.
Lim
,
J.
Zidar
,
D. W.
Cheong
,
S.
Jaenicke
, and
M.
Klähn
,
J. Phys. Chem. B
118
,
10444
(
2014
).
27.
B.
Yoo
,
J. K.
Shah
,
Y.
Zhu
, and
E. J.
Maginn
,
Soft Matter
10
,
8641
(
2014
).
28.
H.
Lee
and
T.-J.
Jeon
,
Phys. Chem. Chem. Phys.
17
,
5725
(
2015
).
29.
M.
Klähn
and
M.
Zacharias
,
Phys. Chem. Chem. Phys.
15
,
14427
(
2013
).
31.
G.
Fragneto
,
Eur. Phys. J.: Spec. Top.
213
,
327
(
2012
).
32.
H. J. C.
Berendsen
,
J. R.
Grigera
, and
T. P.
Straatsma
,
J. Phys. Chem.
91
,
6269
(
1987
).
33.
C.
Oostenbrink
,
A.
Villa
,
A. E.
Mark
, and
W. F.
van Gunsteren
,
J. Comput. Chem.
25
,
1656
(
2004
).
34.
O.
Berger
,
O.
Edholm
, and
F.
Jähnig
,
Biophys. J.
72
,
2002
(
1997
).
35.
S.-W.
Chiu
,
M.
Clark
,
V.
Balaji
,
S.
Subramanian
,
H. J.
Scott
, and
E.
Jacobsson
,
Biophys. J.
69
,
1230
(
1995
).
36.
J. N.
Canongia Lopes
,
J.
Deschamps
, and
A. A. H.
Padua
,
J. Phys. Chem. B
108
,
2038
(
2004
);
J. N.
Canongia Lopes
and
A. A. H.
Padua
,
J. Phys. Chem. B
108
,
16893
(
2004
);
J. N.
Canongia Lopes
,
J.
Deschamps
, and
A. A. H.
Padua
,
J. Phys. Chem. B
108
,
11250
(
2004
).
37.
B. L.
Bhargava
and
S.
Balasubramanian
,
J. Chem. Phys.
127
,
114510
(
2007
);
[PubMed]
T.
Cremer
,
C.
Kolbeck
,
K. R. J.
Lovelock
,
N.
Paape
,
R.
Woelfel
,
P. S.
Schulz
,
P.
Wasserscheid
,
H.
Weber
,
J.
Thar
,
B.
Kirchner
,
F.
Maier
, and
H.
Steinrueck
,
Chem. - Eur. J.
16
,
9018
(
2010
).
38.
J. P. M.
Jämbeck
and
A. P.
Lyubartsev
,
J. Chem. Theory Comput.
8
,
2938
(
2012
);
[PubMed]
N.
Bhatnagar
,
G.
Kamath
, and
J. J.
Potoff
,
J. Phys. Chem. B
117
,
9910
(
2013
);
[PubMed]
A short discussion of the state of the art in lipid modelling is in:
M.
Manna
,
T.
Róg
, and
I.
Vattulainen
,
Biochim. Biophys. Acta
1841
,
1130
(
2014
).
[PubMed]
39.
I. V.
Voroshylova
and
V. V.
Chaban
,
J. Phys. Chem. B
118
,
10716
(
2014
);
[PubMed]
O.
Borodin
,
J. Phys. Chem. B
113
,
11463
(
2009
).
[PubMed]
40.
H.
Berendsen
,
D.
van der Spoel
, and
R.
van Drunen
,
Comput. Phys. Commun.
91
,
43
(
1995
);
E.
Lindahl
,
B.
Hess
, and
D.
van der Spoel
,
J. Mol. Mod.
7
,
306
(
2001
).
41.
B.
Hess
,
H.
Bekker
,
H. J. C.
Berendsen
, and
J. G. E. M.
Fraaije
,
J. Comput. Chem.
18
,
1463
(
1997
).
42.
E.
Chácon
and
P.
Tarazona
,
Phys. Rev. Lett.
91
,
166103
(
2003
);
[PubMed]
F.
Bresme
,
E.
Chácon
,
P.
Tarazona
, and
K.
Tay
,
Phys. Rev. Lett.
101
,
056102
(
2008
).
[PubMed]
43.
W. J.
Allen
,
J. A.
Lemkul
, and
D. R.
Bevan
,
J. Comput. Chem.
30
,
1952
-
1958
(
2009
).
44.
A.
Tardieu
,
V.
Luzzati
, and
F. C.
Reman
,
J. Mol. Biol.
75
,
711
(
1973
).
45.
P. D.
Tieleman
,
J. L.
MacCallum
,
W. L.
Ash
,
C.
Kandt
,
Z.
Xu
, and
L.
Monticelli
,
J. Phys.: Condens. Matter
18
,
S1221
(
2006
).

See also the web site: http://www.ucalgary.ca/tieleman/. The original configuration corresponded to POPE. It was changed to POPC, and the bilayer in water has been re-equilibrated with the POPC potential.

46.
D. M.
Leneveu
,
R. P.
Rand
, and
V. A.
Parsegian
,
Nature
259
,
601
(
1976
);
[PubMed]
T. J.
McIntosh
and
S. A
Simon
,
Annu. Rev. Biophys. Biomol. Struct.
23
,
27
(
1994
).
[PubMed]
47.
S. J.
Marrink
,
M.
Berkowitz
, and
H. J. C.
Berendsen
,
Langmuir
9
,
3122
(
1993
).
48.
K.
Gawrisch
,
H. C.
Gaede
,
M.
Mihailescu
, and
S. H.
White
,
Eur. Biophys. J.
36
,
281
(
2007
).
49.
R. N. A. H.
Lewis
,
B. D.
Sykes
, and
R. N.
McElhaney
,
Biochemistry
27
,
880
(
1988
).
50.
K. R.
Seddon
,
A.
Stark
, and
M.-J.
Torres
,
Pure Appl. Chem.
72
,
2275
(
2000
).
51.
J. L.
Antony
,
E. J.
Maginn
, and
J. F.
Brennecke
,
J. Phys. Chem. B
105
,
10942
(
2001
).
52.
P. A.
Hyslop
,
M.
Morel
, and
R. D.
Sauerheber
,
Biochemistry
29
,
1025
(
1990
).
53.
G.
Pabst
,
M.
Rappolt
,
H.
Amenitsch
, and
P.
Laggner
,
Phys. Rev. E
62
,
4000
(
2000
).
54.
J. F.
Nagle
and
S.
Tristram-Nagle
,
Curr. Opin. Struct. Biol.
10
,
474
(
2000
).
55.
S.
Ludtke
,
K.
He
, and
H.
Huang
,
Biochemistry
34
,
16764
(
1995
).
56.
57.
W.
Rawicz
,
K. C.
Olbrich
,
T.
McIntosh
,
D.
Needham
, and
E.
Evans
,
Biophys. J.
79
,
328
(
2000
).
58.
Q.
Waheed
and
O.
Edholm
,
Biophys. J.
97
,
2754
(
2009
).
59.
L. D.
Landau
and
E. M.
Lifshitz
,
Statistical Physics
(
Addison-Wesley
,
Reading, MA
,
1958
).
60.
N. M.
Philip
,
Proc. Indian Acad. Sci. - Sect. A
9
,
109
(
1939
).
61.
H. L.
Pi
,
J. L.
Aragones
,
C.
Vega
,
E. G.
Noya
,
J. L. F.
Abascal
,
M. A.
Gonzalez
, and
C.
McBride
,
Mol. Phys.
107
,
365
(
2009
).
62.
Z.-Y.
Gu
and
J. F.
Brennecke
,
J. Chem. Eng. Data
47
,
339
(
2002
).
63.
W.
Schrader
,
H.
Ebel
,
P.
Grabitz
,
E.
Hanke
,
T.
Heimburg
,
M.
Hoeckel
,
M.
Kahle
,
F.
Wente
, and
U.
Kaatze
,
J. Phys. Chem. B
106
,
6581
(
2002
).
64.
CRC Handbook of Chemistry and Physics
, 95th ed., edited by
W. M.
Haynes
(
Francis and Taylor
,
Boca Raton
,
2014
).
65.
P. W.
Bridgman
,
Proc. Am. Acad. Arts Sci.
47
,
347
(
1911
);
O. V.
Nagornov
and
V. E.
Chizhov
,
Zhur. Prik. Mek. Tekh. Fiz.
3
,
41
(
1990
).
66.
M.
Marchi
,
J. Phys. Chem. B
107
,
6598
(
2003
).
67.

We considered only non-hydrogen atoms of water and RTIL molecules for consistency with the united atom representation of POPC provided by the Gromos force field.

68.
C. A.
Croxton
,
Statistical Mechanics of the Liquid Surface
(
John Wiley & Sons
,
New York
,
1980
).
69.
R.
Vácha
,
P.
Jurkiewicz
,
M.
Petrov
,
M. L.
Berkowitz
,
R. A.
Böckmann
,
J.
Barucha-Kraszewska
,
M.
Hof
, and
P.
Jungwirth
,
J. Phys. Chem. B
114
,
9504
(
2010
).
70.
T. J.
McIntosh
,
Curr. Opin. Struct. Biol.
10
,
481
(
2000
).
71.
(a)
S. W. I.
Siu
,
R.
Vácha
,
P.
Jungwirth
, and
R. A.
Böckmann
,
J. Chem. Phys.
128
,
125103
(
2008
);
[PubMed]
(b)
W.
Shinoda
,
M.
Shimizu
, and
S.
Okazaki
,
J. Phys. Chem. B
102
,
6647
(
1998
);
(c)
F.
Zhou
and
K.
Schulten
,
J. Phys. Chem
99
,
2194
(
1995
);
(d)
M. A.
Wilson
and
A.
Pohorille
,
J. Am. Chem. Soc.
116
,
1490
(
1994
).
[PubMed]
72.
L. S.
Vermeer
,
B. L.
de Groot
,
V.
Réat
,
A.
Milon
, and
J.
Czaplicki
,
Eur. Biophys. J.
36
,
919
(
2007
).
73.

nx = 128, ny = 64 in Samples #1, #3 and #5; nx = 64, ny = 64 in Samples #2, #4 and #6.

74.
A.
Zangwill
,
Physics at Surfaces
(
Cambridge University Press
,
Cambridge
,
1988
).
75.
R.
Kumar
,
J. R.
Schmidt
, and
J. L.
Skinner
,
J. Chem. Phys.
126
,
204107
(
2007
).
76.
D.
Xenides
,
B. R.
Randolf
, and
B. M.
Rode
,
J. Mol. Liq.
123
,
61
(
2006
).
77.
J. S.
Wilkes
and
M. J.
Zaworotko
,
J. Chem. Soc., Chem. Commun.
1992
,
965
;
A. K.
Abdul-Sada
,
A. M.
Greenway
,
P. B.
Hitchcock
,
T. J.
Mohammed
,
K. R.
Seddon
, and
J. A.
Zora
,
J. Chem. Soc., Chem. Commun.
1986
,
1753
;
C. J.
Dymek
, Jr.
,
D. A.
Grossie
,
A. V.
Fratini
, and
W. W.
Adams
,
J. Mol. Struct.
213
,
25
(
1989
).
78.
J.
Yang
,
C.
Calero
, and
J.
Marti
,
J. Chem. Phys.
140
,
104901
(
2014
).
79.
E.
Flenner
,
J.
Das
,
M.
Rheinstädter
, and
I.
Kosztin
,
Phys. Rev. E
79
,
011907
(
2009
).
80.
W.
Pfeiffer
,
G.
Schlossbauer
,
W.
Knoll
,
B.
Farago
,
A.
Steyer
, and
E.
Sackmann
,
J. Phys. (France)
49
,
1077
(
1988
);
J.
Tabony
and
B.
Perly
,
Biochim. Biophys. Acta
1063
,
67
(
1990
).
81.
W. L. C.
Vaz
,
R. M.
Clegg
, and
D.
Hallmann
,
Biochemistry
24
,
781
(
1985
).
82.
H.
Wennerstrom
and
G.
Lindblom
,
Q. Rev. Biophys.
10
,
67
(
1977
);
[PubMed]
A. L.
Kuo
and
C. G.
Wade
,
Biochemistry
18
,
2300
(
1979
).
[PubMed]
83.
W. L. C.
Vaz
and
P. F.
Almeida
,
Biophys. J.
60
,
1553
(
1991
).
84.
S. Y.
Bhide
and
M. L.
Berkowitz
,
J. Chem. Phys.
123
,
224702
(
2005
).
85.
E.
Falk
,
T.
Róg
,
M.
Karttunen
, and
I.
Vattulainen
,
J. Am. Chem. Soc.
130
,
44
(
2008
).
86.
Y.
von Hansen
,
S.
Gekle
, and
R. R.
Netz
,
Phys. Rev. Lett.
111
,
118103
(
2013
).
87.
J. P.
Hansen
and
I. R.
McDonald
,
Theory of Simple Liquids
(
Academic Press
,
London
,
1986
).
88.
A.
Luzar
and
D.
Chandler
,
Phys. Rev. Lett.
76
,
928
(
1996
);
[PubMed]
A.
Luzar
and
D.
Chandler
,
Nature
379
,
55
(
1996
).
89.
F.
Brochard
,
P. G.
de Gennes
, and
P.
Pfeuty
,
J. Phys.
37
,
1099
(
1976
).
90.
92.
W.-C.
Hung
,
F.-Y.
Chen
,
C.-C.
Lee
,
Y.
Sun
,
M.-T.
Lee
, and
H. W.
Huang
,
Biophys. J.
94
,
4331
(
2008
).
93.
R.
Neumann
,
S. M.
Schiller
,
F.
Gless
,
B.
Grohe
,
K. B.
Hartman
,
I.
Kärcher
,
I.
Köper
,
J.
Lübben
,
K.
Vasilev
, and
W.
Knoll
,
Langmuir
19
,
5435
(
2010
).
94.
See supplementary material at http://dx.doi.org/10.1063/1.4915918 for Table of the Young’s moduliEα, α = x, y and z of the simulated samples; dipole orientation of water molecules along the direction perpendicular to the POPC bilayers (FigS1.eps); charge density and electrostatic potential profiles for sample #1 (FigS2.eps); intrinsic profiles for sample #3 (FigS3.eps); acyl-chain order parametersSCDof all simulated systems (FigS4.eps); snapshots of typical hydration shells around closely associated POPC/[bmim]+ complexes (hydration.xyz file).

Supplementary Material

You do not currently have access to this content.