Lipid bilayer energetics and deformations probed by molecular dynamics computer simulations

Steven O. NielsenDepartment of Chemistry

University of Texas at Dallas1

Harishchandra et al. J. R. Soc. Interface, 7, S15–S26, 2010

Air/water interface in the lung

lipid monolayer

lipid bilayer

lipid bilayer

lipid bilayer

~300 million alveoli in the adult lung

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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3

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---- monolayer ---- bilayer water to lipid ΔG

compress to expand back to0.40 nm2 / Lipid 0.63 nm2 / Lipid

C60

C540 C540

C60

Use a hollow shell (continuum) model

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Water vacuum transfer free energy of fullerenes

fullerene – LJ interaction

Spherical fullerenes have a range of sizesC60 C540

R = 10.5 ÅR = 3.5 Å

• Giant fullerenes found in nano-onions

Carbon 33, 989 (1995)

Particle location in DOPC lipid bilayer

6C60 C80 C240 C320 C540

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Aggregation Behavior in DOPCCan 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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Bending rigidity measurement from the response (force) of a deformed membrane

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Estimated bending rigidity κ from of a DMPC bilayer as a function of the membrane size, L.

S. Kawamoto, T. Nakamura, S. Nielsen, and W. Shinoda, J. Chem. Phys. 139 034108 (2013).

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Lipid Polymorphism: Free Energy Analysis of Vesicle-to-Bicelle Transformation

Fromherz, Chem. Phys. Lett. 94, 259 (1983)edge energy

curvature energy

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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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After a certain cone angle the transformation becomes spontaneous

W. Shinoda, T. Nakamura, and S. Nielsen,Soft Matter 7 9012-9020 (2011).

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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14Partay et al, J. Phys. Chem. B (2010), 114, 10502.

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Acknowledgements

External CollaboratorsRussell DeVane (Procter & Gamble)

Chi-cheng Chiu

FundingSRC Engineering Research Center for Environmentally Benign Semiconductor Manufacturing

Nielsen Lab members

Udayana RanatungaAmir NasrabadiBlake Wilson

Wataru Shinoda (Nagoya U., Japan)

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Coarse Graining

Dipalmitoylphosphatidylcholine (DPPC)

• Coarse-Grain (CG) MD : – reduced number of particles– larger system, longer simulation time

• CG force field developed by Shinoda et al. • 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)

The question of the dispersion and subsequent potency for CNT to form aggregates … is often proposed as an important determinant of their biological effects.

, Boczkowski et al.

One common thread that emerges: toxicity in vivo is modulated by the aggregation of the nanomaterial.

, 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.

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