Transcript Lipid bilayer energetics and deformations probed by molecular dynamics computer simulations Steven O.

Lipid bilayer energetics and deformations probed
by molecular dynamics computer simulations
Steven O. Nielsen
Department of Chemistry
University of Texas at Dallas 1
Air/water interface in the lung
~300 million alveoli in
the adult lung
Harishchandra et al.
J. R. Soc. Interface, 7, S15–S26, 2010
lipid monolayer
lipid bilayer
lipid bilayer
lipid bilayer
One of the most important functions of the
lung surfactant monolayer is to form the first
line of defense against inhaled aerosols such
as nanoparticles.
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compress to
0.40 nm2 / Lipid
---- monolayer
---- bilayer
expand back to
0.63 nm2 / Lipid
water to lipid ΔG
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Spherical fullerenes have a range of sizes
C60
• Giant fullerenes found in
nano-onions
C540
R = 3.5 Å
R = 10.5 Å
Carbon 33, 989 (1995)
Use a hollow shell
(continuum) model
fullerene – LJ interaction
C60
C540
C60
C540
Water  vacuum transfer
free energy of fullerenes
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Particle location in DOPC lipid bilayer
C60
C80
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C240
C320
C540
Aggregation Behavior in DOPC
Can measure aggregation propensity as a function
of size using the solvation free energy method
R= 1.8 Å
R= 2.0 Å
R= 2.5 Å
R= 10 Å
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S. Kawamoto, T. Nakamura, S. Nielsen, and W. Shinoda,
J. Chem. Phys. 139 034108 (2013).
Bending rigidity measurement from the response (force)
of a deformed membrane
Estimated bending rigidity
κ from of a DMPC bilayer
as a function of the
membrane size, L.
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Lipid Polymorphism: Free Energy Analysis
of Vesicle-to-Bicelle Transformation
curvature energy
edge energy
Fromherz, Chem. Phys. Lett. 94, 259 (1983)
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Lipid Polymorphism: Free Energy Analysis
of Vesicle-to-Bicelle Transformation
Measure the response (force) due to a cone potential
that “wedges” open the vesicle.
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W. Shinoda, T. Nakamura, and S. Nielsen,
Soft Matter 7 9012-9020 (2011).
After a certain
cone angle the
transformation
becomes
spontaneous
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The problem is that the chosen reaction coordinate is flawed.
It would be nice if we didn’t need to use a path !!
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Partay et al, J. Phys. Chem. B
(2010), 114, 10502.
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Acknowledgements
Nielsen Lab
Blake
Wilson
members
Amir Nasrabadi
Udayana Ranatunga
Chi-cheng Chiu
External Collaborators
Russell DeVane (Procter & Gamble)
Wataru Shinoda (Nagoya U., Japan)
Funding
SRC Engineering Research Center for Environmentally
Benign Semiconductor Manufacturing
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Coarse Graining
•
Coarse-Grain (CG) MD :
– reduced number of particles
– larger system, longer simulation time
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CG force field developed by Shinoda et al.
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Parameterized against experimental and
atomistic simulation data
– Surface tension
– Transfer free energy
– Membrane structural data
W. Shinoda et al. J. Phys. Chem. B 114, pp 6836–6849 (2010)
Dipalmitoylphosphatidylcholine
(DPPC)
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, Trpkovic et al.
…conclude that the differences in cytotoxic potency and underlying
mechanisms displayed by various fullerene preparations are mainly
due to some physico-chemical characteristics, such as particle size
(surface/volume ratio), surface charge, and aggregation properties.
, Boczkowski et al.
The question of the dispersion and subsequent potency for
CNT to form aggregates … is often proposed as an
important determinant of their biological effects.
One common thread that emerges: toxicity in vivo is
modulated by the aggregation of the nanomaterial.
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