Steven O. Nielsen Department of Chemistry University of Texas at Dallas

1. Lipid bilayer energetics and deformations probed by molecular dynamics computer simulations Steven O. NielsenDepartment of ChemistryUniversity of Texas at Dallas 1

2. 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. 2

4. compress to expand back to 0.40 nm2 / Lipid 0.63 nm2 / Lipid ---- monolayer ---- bilayer water to lipid ΔG

5. C60 C540 • Giant fullerenes found in • nano-onions Use a hollow shell (continuum) model • Spherical fullerenes have a range of sizes R = 3.5 Å R = 10.5 Å Carbon 33, 989 (1995) fullerene – LJ interaction C60 C60 Water  vacuum transfer free energy of fullerenes C540 C540 5

6. 6 Particle location in DOPC lipid bilayer C80 C60 C320 C240 C540

7. Aggregation Behavior in DOPC Can measure aggregation propensity as a function of size using the solvation free energy method R= 2.0 Å R= 1.8 Å R= 2.5 Å R= 10 Å 7

9. 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 κfrom of a DMPC bilayer as a function of the membrane size, L.

10. Lipid Polymorphism: Free Energy Analysis of Vesicle-to-Bicelle Transformation curvature energy edge energy Fromherz, Chem. Phys. Lett. 94, 259 (1983) 10

11. Lipid Polymorphism: Free Energy Analysis of Vesicle-to-Bicelle Transformation Measure the response (force) due to a cone potential that “wedges” open the vesicle.

12. W. Shinoda, T. Nakamura, and S. Nielsen,Soft Matter 7 9012-9020 (2011). After a certain cone angle the transformation becomes spontaneous

13. The problem is that the chosen reaction coordinate is flawed. It would be nice if we didn’t need to use a path !!

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

15. Acknowledgements Nielsen Lab members Blake Wilson Amir Nasrabadi UdayanaRanatunga Chi-cheng Chiu External Collaborators Russell DeVane (Procter & Gamble) WataruShinoda(Nagoya U., Japan) Funding SRC Engineering Research Center for Environmentally Benign Semiconductor Manufacturing

16. Coarse Graining • 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 Dipalmitoylphosphatidylcholine (DPPC) W. Shinoda et al. J. Phys. Chem. B 114, pp 6836–6849 (2010)

17. , 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. 17