Phase transition of a DPPC bilayer induced by an external surface pressure: from bilayer to monolayer behavior. a molecular dynamics simulation study.
ABSTRACT Understanding the lipid phase transition of lipid bilayers is of great interest from biophysical, physicochemical, and technological points of view. With the aim of elucidating the structural changes that take place in a DPPC phospholipid bilayer induced by an external isotropic surface pressure, five computer simulations were carried out in a range from 0.1 to 40 mN/m. Molecular dynamics simulations provided insight into the structural changes that took place in the lipid structure. It was seen that low pressures ranging from 0.1 to 1 mN/m had hardly any effect on the structure, electrical properties, or hydration of the lipid bilayer. However, for pressures above 40 mN/m, there was a sharp change in the lipid-lipid interactions, hydrocarbon lipid fluidity, and electrostatic potential, corresponding to the mesomorphic transition from a liquid crystalline state (L(alpha)) to its gel state (P'(beta)). The head lipid orientation remained almost unaltered, parallel to the lipid layer, as the surface pressure was increased, although a noticeable change in its angular distribution function was evident with the phase transition.
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ABSTRACT: Phase behavior of lipid bilayers at high pressure is critical to biological processes. Using coarse grained molecular dynamic simulations, we report critical characteristics of dipalmitoylphosphatidylcholine bilayers with applied high pressure, and also show their phase transition by cooling bilayer patches. Our results indicate that the phase transition temperature of dipalmitoylphosphatidylcholine bilayers obviously shifts with pressure increasing in the rate of 37 °C kbar(-1), which are in agreement with experimental data. Moreover, the main phase transition is revealed to be strongly dependent on lipid area. A critical lipid area of ~0.57 nm(2) is found on the main phase transition boundary. Similar structures of acyl chains lead to the same sensitivity of phase transition temperature of different lipids to the pressure. Based on the lateral density and pressure profiles, we also discuss the different effects on bilayer structure induced by high temperature and high pressure, e.g., increasing temperature induces higher degree of interdigitation of lipid tails and thinner bilayers, and increasing pressure maintains the degree of interdigitation and bilayer thickness.Physical Chemistry Chemical Physics 03/2012; 14(16):5744-52. · 3.83 Impact Factor
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ABSTRACT: While the surface tension of a cell membrane, or a plasma membrane, regulates cell functions, little is known about its effect on the conformational changes of the lipid bilayer and hence the resulting changes in the cell membrane. To obtain some insights into the phase transition of the lipid bilayer as a function of surface tension, we used a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer as a model lipid bilayer and aquaporin (AqpZ), a transmembrane channel protein for water, as a model embedded protein. A coarse-grained molecular dynamics simulation was applied to illustrate the phase transition behavior of the pure DPPC bilayer and aquaporin-embedded DPPC bilayer under different surface tensions. It was shown that an increased surface tension reduced the phase transition temperature of the DPPC bilayer. As for the DPPC bilayer in gel form, no significant changes occurred in the structure of the bilayer in response to the surface tension. Once in a liquid crystal state, both the structure and properties of the DPPC bilayer, such as area per lipid, lipid order parameters, bilayer thickness and lateral diffusion coefficients, were responsive to the magnitude of surface tension in a linear way. The presence of aquaporin attenuated the compact alignment of the lipid bilayer, hindered the parallel movement, and thus made the DPPC bilayer less sensitive to the surface tension.Physical Chemistry Chemical Physics 03/2014; · 3.83 Impact Factor
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ABSTRACT: An atomistic-level understanding of cationic lipid monolayers is essential for development of gene delivery agents based on cationic micelle-like structures. We employ molecular dynamics (MD) simulations for a detailed atomistic study of lipid monolayers composed of both pure zwitterionic dipalmitoylphosphatidylcholine (DPPC) and a mixture of DPPC and cationic cetyltrimethylammonium bromide (CTAB) at the air/water interface. We aim to investigate how the composition of the DPPC/CTAB monolayers affects their structural and electrostatic properties in the liquid-expanded phase. By varying the molar fraction of CTAB, we found the cationic CTAB lipids have significant condensing effect on the DPPC/CTAB monolayers, i.e., at the same surface tension or surface pressure, monolayers with higher CTAB molar fraction have smaller area per lipid. The DPPC/CTAB monolayers are also able to achieve negative surface tension without introducing buckling into the monolayer structure. We also found the condensing effect is caused by the interplay between the cationic CTAB headgroups and the zwitterionic phosphatidylcholine (PC) headgroups which has electrostatic origin. With CTAB in its vicinity, the P-N vector of PC headgroups reorients from being parallel to the monolayer plane to a more vertical orientation. Moreover, detailed analysis of the structural properties of the monolayers, such as the density profile analysis, hydrogen bonding analysis, chain order parameter calculations and radial distribution function calculations were also performed for better understanding of cationic DPPC/CTAB monolayers.The Journal of Physical Chemistry B 09/2014; · 3.61 Impact Factor
Phase Transition of a DPPC Bilayer Induced by an External Surface
Pressure: From Bilayer to Monolayer Behavior. A Molecular
Dynamics Simulation Study
J. J. Lo ´pez Cascales,*,†T. F. Otero,†A. J. Ferna ´ndez Romero,†and L. Camacho‡
Centro de Electroquı ´ca y Materiales Inteligentes (CEMI), UniVersidad Polite ´cnica de Cartagena,
Aulario II, Campus de Alfonso XIII, 30203 Cartagena, Murcia, Spain, and Depto. Quı ´mica Fı ´sica,
UniVersidad de Co ´rdoba, Edi. Marie Curie, Campus de Rabanales, 14014 Co ´rdoba, Spain
ReceiVed January 24, 2006. In Final Form: April 20, 2006
Understanding the lipid phase transition of lipid bilayers is of great interest from biophysical, physicochemical,
and technological points of view. With the aim of elucidating the structural changes that take place in a DPPC
phospholipid bilayer induced by an external isotropic surface pressure, five computer simulations were carried out
in a range from 0.1 to 40 mN/m. Molecular dynamics simulations provided insight into the structural changes that
took place in the lipid structure. It was seen that low pressures ranging from 0.1 to 1 mN/m had hardly any effect
on the structure, electrical properties, or hydration of the lipid bilayer. However, for pressures above 40 mN/m, there
to the mesomorphic transition from a liquid crystalline state (LR) to its gel state (P′?). The head lipid orientation
remained almost unaltered, parallel to the lipid layer, as the surface pressure was increased, although a noticeable
change in its angular distribution function was evident with the phase transition.
points of view because of their important role played in the
structure and function of biological membranes.1The phase
transition in anhydrous or fully hydrated lipid bilayers can be
induced simply by variations in pressure when the temperature
is held constant. Thus, increasing pressure on fully hydrated
transition temperature (Tm) results in the sequential conversion
of their liquid crystalline state phase (LR) into their different gel
phases at atmospheric pressure. Hence, in the case of DPPC
(dipalmitoylphosphatidylcholine) phospholipids, the phase tran-
sition temperature Tmincreases as the pressure increases.
living cells of marine organisms living at great depths (inver-
tebrates and fishes) or some diving mammals (mainly pinnipeds
and cetaceans) which are able to dive to great depths.2,3In this
regard, the study of the lipid barometric mesomorphism of
biological membranes is important from biochemical2, biophysi-
cal, and physicochemical points of view to understand how
animals that live at such depths have evolved mechanisms to
counteract these pressure-induced problems and thus, for the
modifications of membrane-bound proteins,4,5membrane ion
channels,6,7and the membrane structure,8-12including altering
the enzyme structure at the active sites so that the pressure does
not change the affinity of the enzyme for its substrate and in
phospholipid bilayer to counteract the effects of the elevated
pressures. In this regard, by comparing the thermotropic and
as a powerful tool for looking at the structure and dynamics of
phospholipid bilayers in atomic detail. Since the preliminary
works of Berendsen et al.,14a great number of papers have been
published,15-21favored by increasing computing power and
improvements in simulation algorithms. Hence, using the same
methodology as employed by the above-mentioned authors and
by ourselves, we will describe the effect of an isotropic surface
coupling pressure on the phase transition of a DPPC bilayer. In
addition, we will compare our results with experimental results
for DPPC bilayers and DPPC monolayers at the air-water
interface. In this sense, we wish to mention the work of Feller
* To whom correspondence should be addressed. E-mail: javier.lopez@
†Universidad Polite ´cnica de Cartagena.
‡Universidad de Co ´rdoba.
(1) Yeagle,P.,Ed.;ThestructureofBiologicalMembranes;CRCPress: Boca
Raton, FL, 1991.
(2) Castellini, M.; Rivera, P.; Castellini, J. Comp. Biochem. Physiol. Part A
2002, 133, 893-899.
(3) Bartlett, D. Biochim. Biophys. Acta 2002, 1595, 367-381.
(4) Tauc, P.; Mateo, C. R.; Bronchon, J.-C. Biochim. Biophys. Acta 2002,
(5) Scarlata, S. Braz. J. Med. Biol. Res. 2005, 38, 1203-1208.
(6) Zhu, F.; Tajkhorshid, E.; Schulten, K. Biophys. J. 2002, 83, 154-160.
(7) Kato, M.; Hayashi, R.; Tsuda, T.; Taniguchi, K. Eur. J. Biochem. 2002,
(8) Kato, M.; Hayashi, R. Biosci., Biotechnol., Biochem. 1999, 63 (8), 1321-
(9) Macdonald, A.; Fraser, P. Comp. Biochem. Physiol. Part A 1999, 122,
(10) Macdonald, A. Biochim. Biophys. Acta 2002, 1595, 387-389.
(11) Cantor, R. J. Phys. Chem. B 1997, 101 (10), 1723-1725.
(12) Gullingsrud, J.; Schulten, K. Biophys. J. 2004, 86, 3496-3509.
(13) Frenkel, D.; Smit, B. Understanding Molecular Simulations; Academic
Press: New York, 2002.
(15) Egberts, E.; Marrink, S. J.; Berendsen, H. J. C. Eur. Biophys. J. 1994,
22 (6), 423-436.
(16) Lo ´pez Cascales, J. J.; Garcı ´a de la Torre, J.; Marrink, S.; Berendsen, H.
J. Chem. Phys. 1996, 104 (7), 2713-2720.
(17) Pandit, S.; Bostick, D.; Berkowitz, M. Biophys. J. 2003, 84 (6), 3743-
(18) Pandit, S.; Bostick, D.; Berkowitz, M. Biophys. J. 2003, 85 (5), 3120-
(19) P. Mukhopadhyay, L. M.; Tieleman, D. Biophys. J. 2004, 86 (3), 1601-
(20) Sachs, J.; Nanda, H.; Petrache, H.; Woolf, T. Biophys. J. 1980, 86 (6),
(21) Cascales, J. L.; Otero, T.; Smith, B.; Gonzalez, C.; Marquez, M. J. Phys.
Chem. B 2006, 110 (5), 2358-2363.
Langmuir 2006, 22, 5818-5824
10.1021/la0602315 CCC: $33.50© 2006 American Chemical Society
Published on Web 05/27/2006
These authors simulated a DPPC monolayer at the water/air
interface formed by two leaflets in a vacuum where the lipid
the lipid layer (XY plane) and the periodicity was cut along the
perpendicular axis to the lipid layer (Z axis).
In this regard, we reproduced the main phase transition of
DPPC lipid bilayers from their liquid crystaline phase LRto its
gel phase P′?, to the pressure of 40 mN/m, at the simulation
of 314.4 K24,25for pure DPPC in aqueous solution. From
appreciated severe discrepancies between both systems, till the
pressure corresponding to the phase transition was achieved.
2. Methods and Model
A periodical three dimension computing box composed of 72
DPPC phospholipids, Figure 1, split into two leaflets of 36 DPPC
each, was generated. The DPPC were placed with the phospholipid
heads pointing toward the middle of the computing box. The gap
between the two lipid leaflets was filled with water from an
equilibrated computing box containing 216 water molecules of the
SPC/E water model.26Hence, the system was formed of 72 DPPC
water molecules, which amounted a total of 11151 atoms. Figure
2 depicts some snapshots of the system after 20 ns of simulation,
for different pressures. In this regard, we remark that, assuming the
fact that to place the lipids in the middle or in opposite sides of the
computing box is equivalent for the final conclusions (due to the
periodicity of the computing box), in our case, we preferred the
approaches a bit better the structure of a symmetric monolayer.
Once the system was generated, the whole computing box was
submitted to a steepest descent energy minimization process to
remove overlaps between neighboring atoms and stressing bonds.
The system was then ready for starting the simulation.
To simulate the external surface coupling pressure, the system
(surface tension coupling) and a normal coupling pressure on the
axis perpendicular to the lipid plane. In this case, the pressure was
coupled to a pressure bath using the Berendsen pressure coupling
algorithm,27with a coupling constant of τp) 0.1 ps, for the normal
and surface pressure coupling. This method is based on the fact that
the pressure can be defined by a tensor
(x, y, or z), V is the volume, mithe mass of the particle i, ViRis the
velocity in the R direction, FijRthe R component of the total force
on the particle i due to the particle j, and rij?is the ? component of
the vector ri- rj. Thus, the kinetic contribution to the pressure is
given by the first term in eq 1, and the virial contribution is given
by the second. The three diagonal elements in the pressure tensor
tensor has been defined by Equation 1, Berendsen et al.27proposed
the weak coupling algorithm to rescale the coordinates and box
vectors every time step with a matrix µ, which has the effect of a
The scaling matrix µ is given by
where the tensor ? is the isotermal compressibility of the system.
In this regard, the velocities assigned to each particle of the system
are not scaled. In an isotropical system, the pressure P is calculated
from the diagonal matrix of the pressure tensor of eq 1 as the trace
of (Pxx+ Pyy+ Pzz)/3 for obtaining the scaling matrix. For instance,
for systems with interfaces (like in our case), semi-isotropic scaling
can be used. In this case, the x and y directions (which corresponds
to the membrane plane) are isotropical and the z direction is scaled
normal pressure of 1 atm (perpendicular to the bilayer plane) and
correspond to 0.1, 0.17, 1, 10, and 40 mN/m respectively.
The system was also coupled to an external temperature bath of
330 K above the gel-liquid crystalline phase transition temperature
Tmof a DPPC bilayer24,25at 1 atm of isotropic pressure, with a
coupling constant of τT) 0.1 ps.27
GROMACS 3.1.128,29was used to run the MD simulations. The
DPPC force field was the same as that used by Egberts et al. in
previous simulations.15The long-range interactions were simulated
by a Lennard-Jones potential and the electrostatic interactions by
the Ewald algorithm.30,31A time step of 4 fs (fs) was used in the
five simulations, each of 20 nanoseconds (ns). All of the bonds of
the system were constrained by the SHAKE32algorithm.
(22) Feller, S.; Zhang, Y.; Pastor, R.; Brooks, R. J. Chem. Phys. 1995, 103
(23) Kaznessis, Y.; Kim, S.; Larson, R. Biophys. J. 2002, 82, 1731-1742.
(24) Lewis, R.; Mark, N.; McElhaney, R. Biochemistry 1987, 26 (19), 6118-
(25) Young, L. R. D.; Dill, K. A. Biochemistry 1993, 27 (14), 5281-5289.
(26) Berendsen, H.; Grigera, J.; Straatsma, T. J. Phys. Chem. 1987, 91 (24),
(27) Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.; DiNola, A.;
Haak, J. R. J. Chem. Phys. 1984, 8 (8), 3684-3690.
(28) Berendsen, H.; van der Spoel, D.; van Drunen, R. Comput. Phys. Comm.
1995, 91 (1-3), 43-56.
(29) Lindahl, E.; Hess, B.; van der Spoel, D. J. Mol. Model. 2001, 7 (8),
(31) Essmann, U.; Perea, L.; berkowitz, M.; Darden, T.; Lee, H.; Pedersen,
L. J. Chem. Phys. 1995, 103 (19), 8577-8593.
(32) van Gunsteren, W.; Berendsen, H. Mol. Phys. 1977, 34 (5), 1311-1327.
Figure 1. Atom numeration of a DPPC lipid molecule used in this
Phase Transition of a DPPC Bilayer Langmuir, Vol. 22, No. 13, 2006 5819
Simulations were carried out on an HP parallel computer on a
node with four processors, and 5 days of intensive computing work
was required for each one of the five cases studied.
3. Results and Discussion
3.1. Lipid Area. To avoid erroneous conclusions related to
simulation artifacts, the surface area per lipid molecule was
monitored along the simulated trajectory, such as depicted in
From our results, we observe how the first 5 ns of simulations
must be discarded from the analysis because the system has not
yet reached an equilibrated state. This equilibration time was
extended to 10 ns when the coupling pressure was 40 mN/m.
These results are in a perfect accordance with the recently
published values of De Vries et al.,33who found that the surface
area of a bilayer containing 36 lipids per leaflet converged to a
steady value after a period of 3-5 ns. The dimensions of the
7.14), (4.87,4.82,7.06), (4.65,4.61,7.71), and (3.95,3.94,10.27),
for the (x,y,z) axis of the computing box in nm, and 0.1, 0.17,
1, 10, and 40 mN/m, respectively.
The first part of the simulated trajectories was discarded from
the analysis, and Figure 4 depicts the surface area per lipid at
of lipid surfaces corresponding to bilayers and monolayers.
In the simulation, two limit behaviors can be observed for
DPPC bilayers: at low pressures, between 0.1 and 0.17 mN/m
area of 0.66 nm2at 330 K, which agrees with the reported
experimental data of a DPPC bilayer, concerning the spread of
values that depend on the experimental technique used. These
state (LR), as mentioned by Nagle et al.34in their review on the
structure of lipid bilayers. When the surface pressure was raised
(33) de Vries, A.; Chandrasekhar, I.; van Gunsteren, W.; Hunenberger, P. J.
Chem. Phys. B 2005, 109 (23), 11643-11652.
Figure 2. Snapshots of the system after 20 ns of simulation, corresponding to 0.1, 1, 10, and 40 mN/m. In the snapshot D, we can observe
the alignament of the lipid tails characteristic of lipid gel phase (P′?).
Figure 3. Running area of a DPPC molecule subjected to different
coupling pressures. We observe how for simulation times above
5000 ps the system achieve a steady surface area, except in the case
of P ) 40mN/m in which 10 000 ps are required to equilibrate the
to different external pressures: (circles) simulations, (squares)
5820 Langmuir, Vol. 22, No. 13, 2006Lo ´pez Cascales et al.
to 10 or 40 mN/m (60 and 225 atm, respectively), the surface
area reproduced the experimental value of a DPPC monolayer
in a water/air interface, for which a value of 0.57 and 0.44 nm2
has been reported experimentally35at 298 K. This value is also
close to the value obtained by simulation by Kaznessis et al.23
for DPPC monolayers, where a value of 0.55 nm2was estimated
for a pressure of 18 mN/m. Hence, the model describes quite
The difference in surface area between DPPC bilayers and
monolayers has been related to the lipid bilayer interdigitation
that occurs between both leaflets of the lipid bilayer when the
terminal methyl groups of the acyl lipid chains extend beyond
the bilayer midplane.1,34In Figure 5, we observe how this effect
is reduced by increasing the surface pressure in the membrane.
Thus, the difference in density between the CH3of lipid tails
corresponding to opposite leaflets, increases with the surface
pressure in the membrane (such as it should correspond to a
lower interdigitation), in good agreement with the behavior
proposed by Nagle et al.34when a phase transition takes place.
As a consequence of the interdigitation of lipid tails of opposite
leaflets in the bilayer, a reduction in the entropy of the system
is expected due to a diminution of the freedom of motion of the
lipid tails, and as a consequence, the free energy increases (∆G
) ∆H - T∆S, where ∆G corresponds to the free energy, ∆H
to the enthalpy, T the temperature, and ∆S the entropy) and,
hence, a shift in the thermodynamic properties of the system
(including the phase transition of lipid bilayers) compared with
lipid monolayers. In this regard, by raising the surface pressure,
the interdigitation effects in the bilayers are minimized due to
in part to the reduction of the freedom in the motion of the lipid
tails (associated to the phase transition of the lipid adopting a
hexagonal packing, such as we will discuss below) and in part
to a reduction of the interdigitation between the lipid tails of
opposite leaflets. Hence, in this case, for pressures high enough
beyond the phase transition, lipid bilayers and monolayers are
expected to behave similarly.
3.2. DPPC Head Structure. To obtain insight into the
differences in the lipid head conformations of the lipid bilayers
subjected to different surface pressures, Figure 6 depicts the
angular distribution function g(θ) of the lipid heads at different
surface pressures. The angle θ was defined as the angle between
the vector P-N (corresponding to atoms 8 and 4 of Figure 1,
respectively) of each lipid head and the normal axis of the lipid
From Figure 6, we observe how the shape of the angular
pressure was raised. However, when the pressure reached 40
mN/m, the angular distribution function adopted a narrower
distribution shape. However, apart from this, in all cases the
DPPC head orientation remained almost parallel to the lipid/
values of 85, 82, 83, 83, and 85° were obtained for the mean
value of the head phospholipid orientation, corresponding to the
pressures of 0.1, 0.17, 1, 10, and 40 mN/m, respectively. These
values obtained for DPPC by simulation agree with the values
measured for DPPC bilayers in their liquid crystalline state,17
where values of 78 ( 21° were measured for different
concentrations of electrolyte. Analogous results were obtained
by Dluhy36for monolayers of DPPC at a wide range of surface
pressures, in all cases, the head orientation remaining almost
parallel to the lipid surface.
3.3. Lipid Hydration and Lipid-Lipid Interactions. The
radial distribution function g(r) is often employed to identify
close interactions between neighboring atoms. In this respect,
the radial distribution function g(r) is defined as
r and thickness δr from a reference atom and F is the number
Thus, from Figure 7, the oxygen hydration of some oxygen
groups of the DPPC lipids can be depicted as a function of the
surface pressure. It can be seen how, for the phosphate oxygen
group, almost no variation in its hydration was observed when
the pressure was increased. On the other hand, the deepest
carboxyl oxygens of the lipid tails (atom 35 of Figure 1) showed
dehydration, as a result of the hexagonal structure adopted by
the collective packing, such as we will describe below. From
numerical integration of the first coordination peak of the radial
distribution function, we were able to evaluate the number of
water molecules surrounding the different atoms studied. Thus,
2.04, 2.07, 2.05, 1.99, and 1.86 water molecules were computed
for phosphate oxygen (atom 10, Figure 1), corresponding to
(35) Hunt, R.; Mitchell, M.; Dluhy, R. J. Mol. Struct. 1989, 214, 93-109. (36) Dluhy, R. Appl. Spectrosc. ReV. 2000, 35 (4), 315-351.
Figure 5. CH3distribution of lipid tails corresponding to lipids of
opposite leaflets in the bilayer (solid or dashed line) at different
surface pressures: (a) 0.1, (b) 10, and (c) 40 mN/m.
(corresponding to the atoms 8 and 4 of the Figure 1, respectively)
g(θ), for P ) 40mN/m,which is associated to the phase transition
of the lipids.
Angular distribution function of the P-N vector
Phase Transition of a DPPC BilayerLangmuir, Vol. 22, No. 13, 2006 5821
pressures of 0.1, 0.17, 1, 10, and 40 mN/m, respectively. These
values agree with the value of 2.5 proposed by Marrink37for a
simulation carried out with DPPC bilayers at 335 K and 0.17
mN/m and with the 2.2 obtained for a DPPS bilayer at 350 K
and 0.17 mN/m.38As regards the tail carbonyl oxygens (atom
35, Figure 1), values of 1.13, 1.14, 1.12, 1.06, and 0.72 water
to 40 mN/m result in a dehydration of 40% in the carbonyl
oxygen of the lipid tails compared with the 10% observed for
the oxygen phosphate group. From Figure 7c, the number of
hydrating water molecules around the phosphorus atom (atom
8, Figure 1) can be estimated. Thus, from numerical integration
of the radial distribution function, we obtained 5.48, 5.51, 5.45,
5.30, and 4.90 water molecules for the first hydration shell
corresponding to pressures of 0.1, 0.17, 1, 10, and 40 mN/m,
respectively. In this respect and considering the phosphate and
carbonyl oxygen groups, hydration of the lipid (estimated as the
sum of the hydration number of the phosphate group plus the
obtained for a monolayer of DMPC (dimyristoylphosphatidyl-
choline) by d’Acapito et al.39were 8.6 water molecules/lipid at
low pressures, which agrees with our results of 7.74 water
molecules/lipid, if we take into consideration the difference in
temperatures (298 K compared with our 330 K) and the limited
Unfortunately, we have been unable to find any information
relating DPPC dehydration with the surface pressure. However,
experimentally, Schalke et al.40observed that the hydration of
DMPA (dimyristoylphosphatidyl acid) monolayers from low to
high pressures corresponded to one water molecule/lipid, which
agrees with our estimations from the simulation.
perturbs the lipid-water interface, Figure 8 depicts the atomic
density across the lipid-water interface. The carboxyl oxygen
of the phosphate group and lipid tails for pressures of 0.17 and
water penetrates beyond both the oxygens mentioned above at
(case c), water is expelled from the carboxyl lipid tail, in good
agreement with the hydration numbers obtained from the radial
distribution function of the DPPC carbonyl oxygen group of the
lipid tails. In this regard, some experimental results34evidenced
an increase in the thickness of the lipid/water interface for the
with the qualitative results of Figure 8c, where a broader
distribution of the lipid/water interface is obtained compared
with that depicted in panels a and b of Figure 8, where the
differences can be associated to the phase transition of the lipid
bilayer from its liquid crystaline (LR) to its gel phase (P′?).
Furthermore, Figure 9 depicts the radial distribution function
of the phosphate and carbonyl oxygens of the lipid tails around
the phosphorus of a neighboring DPPC. Figure 9a depicts how
as corresponds to a pressure of 40 mN/m, P-O charge bridges
emerged between neighboring lipids. The same behavior was
described by both, phosphate and carbonyl oxygens, although
to 40 mN/m. In both cases (panels a and b of Figure 9), the
strengthening of the charge bridges between P and oxygens of
neighboring lipids partly compensated the dehydration of the
lipid, as was discussed above.
Thesis; Rijkuniversiteit Groningen: The Netherlands, 1994.
(38) Lo ´pez Cascales, J. J.; Berendsen, H. J. C.; Garcı ´a de la Torre, J. J. Phys.
Chem. 1996, 100 (21), 8621-8627.
(39) d’Acapito, F.; Emelianov, I.; Reilini, A.; Cavatorta, P.; Gliozzi, A.;
Minicozzi, V.; Morante, S.; Solari, P.; Rolandi, R. Langmuir 2002, 18 (13),
(40) Schalke, M.; Kruger, P.; Weygand, M.; Losche, M. Biochim. Biophys.
Acta 2000, 1464 (1), 113-126.
Figure 7. Radial distribution function of water (considering the
water oxygen) around several lipid oxygens and pressures: (a)
Oxygen carbonyl tail (atom number 35, Figure 1), (b) phosphate
number 8, Figure 1).
Figure 8. Distribution of water, phosphorus (atom 8 Figure 1),
phosphate oxygen group (atom 10, Figure 1), and carbonyl oxygen
group (atom 35, Figure 1) across the phospholipid/water interface,
at three different pressures: (a) 0.17, (b) 10, and (c) 40 mN/m.
atoms of neighboring lipids, for different surface pressures. (a)
Phosphate oxygen (atom 10, Figure 1) and (b) carbonyl oxygen of
the lipid tails (atom 35, Figure 1).
5822 Langmuir, Vol. 22, No. 13, 2006 Lo ´pez Cascales et al.
3.4. Hydrocarbon Tail Structure. The deuterium order
parameter (-SCD) determined from NMR experiments gives an
indication of the order in the membrane. It is associated with the
respect to the transverse plane of the membrane. The order
paramenter, -SCD, can be determined from simulation for an
where Sxxand Syyare the terms of the order parameter tensor S
where x, y, and z are the local coordenates of the system and the
angle θ is the angle between the membrane normal (z axis) and
the plane spanned by the two C-D vectors of the ith C atom.
Since in our simulations we do not represent explicitely the
hydrogen atoms, the angle θ is defined by the vector from the
i - 1 to i + 1 C atoms and the bilayer normal (z axis).
Thus, Figure 10 depicts the variation in the order parameter
of the lipid tails related to different surface pressures.
From Figure 10, we observe good agreement between low
pressures (roughly from 0.1 to 1.0 mN/m) and the experimental
data of DPPC bilayers41at 330 K and42at 324 K above the
the experimental data from ref 42 and our simulation data is
simulation and experimental data when the pressure increases
to 40 mN/m, in which case, a diminution in the fluidity of the
hydrocarbon layer (or an increase in the order of the membrane)
becomes evident as corresponds to the phase transition from its
liquid crystalline (LR) to its gel (P′?) phase.
In this respect, the tilt angle of the lipid tails in monolayers
can be estimated experimentally at high pressures from ATR-
IR measurements. Under these conditions, an angle of 70° has
been measured.36Thus, considering the angle θ as the angle
between the direction of a chain segment and the bilayer normal
(z axis), the molecular order parameter41of the lipid tails is
related to the average orientation according to
〈-SCDmol〉 )〈3(cos θ)2- 1
where the angular brackets indicate the time average. Thus,
considering the average angle of 70° for the mean θ angle of the
hydrocarbon lipid tails, a value of 0.32 is estimated for the
molecular order parameter. This value agrees with the mean
value of 0.34 obtained from our simulations, calculated as an
average of the order parameters through the lipid tails.
lipid tails, a plot of the X-Y hydrocarbon lipid tails of one of
the two leaflets is depicted in Figure 11, where each of the dots
in the Figure 11 was calculated as the center of mass of the
ethylene lipid tails. In Figure 11, we observe the hexagonal
lipid packing in its gel phase (P′?), which agrees with the
and FT-IR measurements43,44of DPPC bilayers and DPPC
monolayers in its gel phase.
3.5. Electrostatic Potential. Monolayers of different phos-
pholipids are of undoubted interest from a technological point
of view because they can be used to create modified electrodes.
potential across a lipid/water interface can be modified by a
surface coupling pressure. From the atomic density across the
the same interface.
Thus, the electrostatic potential ψ across the DPPC bilayer
was computed by a double integral of the charge density (F)
across the bilayer45as follows:
where the origin z of the electrostatic potential ψ(0) is taken at
in this way agrees with the computed charge density using
Poisson’s equation, without using a cutoff radius.17
Thus, Figure 12 depicts the electrostatic potential across one
of the two symmetric lipid leaflets. From Figure 12, we observe
(41) Seelig, A.; Seelig, J. Biochemistry 1974, 13 (23), 4839-4845.
(42) Brown, M. F. J. Phys. Chem. 1982, 86 (3), 1576-1599.
(44) Winter, R. Curr. Opin. Colloid Interface Sci. 2001, (6), 303-312.
(45) van Buuren, A.; Berendsen, H. Langmuir 1994, 10 (6), 1703-1713.
Figure 10. Order parameter (-SCD) along ethylene lipid tails for
several pressures. The order parameters were averaged on both
lipid tails. O and 4 correspond to experimental results obtained for
DPPC bilayers in its liquid crystaline phase, see refs 41 and 42,
SR?)〈3 cos θRcos θ?- δR?〉
R ) x, y, z; ? ) x, y, z
Figure 11. Lipid tail packing for one of the two DPPC leaflets of
the membrane obtained from the center of mass of the ethylene
groups of the lipid tails. (a) Pressure of 0.1 mN/m and (b) pressure
of 40 mN/m. The hexagonal packing in panel b corresponds to the
lipid packing in its gel phase P′?.
ψ(z) - ψ(0) ) -1
Phase Transition of a DPPC BilayerLangmuir, Vol. 22, No. 13, 2006 5823
how the shape of the electrostatic potential remains almost
point the phase transition from the liquid crystalline to the gel
state takes place. Thus, the potential difference measured from
our simulations ranges from 0.7 to 0.85 V, which is in good
agreement with experimental results of DPPC monolayers
measured by Caetano et al.46where values between 0.60 and
0.65 V were obtained. These authors associated this variation in
there is a variation in the shape of the orientational distribution
function with the pressure (due to reorientation of the water
dipole vector in the lipid/water interface20) which could explain
the observed behavior.
4. Conclusions and Closing Remarks
A study of the barometric phase transition of lipid bilayers is
of great relevance from biophysical, physicochemical, and
technological points of view. Thus, raising the surface pressure
among other properties, the lipid dehydration was evident for
pressures above the phase transition. From our simulations, we
from liquid crystalline state (LR) to its gel state (P′?) as 1 water
When the pressure was high enough to induce the phase
transition, important interactions emerged between neighboring
how interactions between the phosphorus and oxygen of the
phosphate group of neighboring lipids increased only when the
phase transition took place, unlike in the phosphorus and tail
were observed, even above their phase transition.
Another important change in the lipid structure is related to
the fluidity of the ethylene lipid tails. Thus, for pressures below
10 mN/m, almost no variation in the fluidity of the hydrocarbon
region was observed. When the pressure approached 40 mN/m,
the order parameter of the lipid tails increased and the packing
of the lipid tails changed from a disordered to an hexagonal
LRto its gel phase, P′?.
Finally, we conclude that the methodology used in this work
permits us to predict the behavior lipid monolayers, only for
pressures beyond the lipid phase transition.
Acknowledgment. J.J.L.C., A.J.F.R., and T.F.R. thank the
Ministerio de Educacion y Ciencia and the Fundacion Seneca
(46) Caetano, W.; Ferreira, M.; Tabak, M.; Sanchez, M. M.; Oliveira, O.;
Kru ¨ger, P.; Schalke, M.; Lo ¨sche, M. Biophys. Chem. 2001, 91 (1), 21-35.
Figure 12. Electrostatic potential across the DPPC/water bilayer.
The zero is placed in the middle of the lipid bilayer.
5824 Langmuir, Vol. 22, No. 13, 2006 Lo ´pez Cascales et al.