Lipid bilayer energetics and deformations probed by molecular dynamics computer simulations Steven O. Nielsen Department of Chemistry University of Texas at Dallas 1

Harishchandra et al. J. R. Soc. Interface, 7, S15–S26, 2010 Air/water interface in the lung lipid monolayer 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. 2

3

monolayer ---- bilayer water to lipid ΔG compress to expand back to 0.40 nm 2 / Lipid 0.63 nm 2 / Lipid

C 60 C 540 C 60 Use a hollow shell (continuum) model 5 Water  vacuum transfer free energy of fullerenes fullerene – LJ interaction Spherical fullerenes have a range of sizes C 60 C 540 R = 10.5 ÅR = 3.5 Å Giant fullerenes found in nano-onions Carbon 33, 989 (1995)

Particle location in DOPC lipid bilayer 6 C 60 C 80 C 240 C 320 C 540 6

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 ÅR= 10 Å 7

8

Bending rigidity measurement from the response (force) of a deformed membrane 9 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 (2013).

10 Lipid Polymorphism: Free Energy Analysis of Vesicle-to-Bicelle Transformation Fromherz, Chem. Phys. Lett. 94, 259 (1983) edge energy curvature energy 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 After a certain cone angle the transformation becomes spontaneous W. Shinoda, T. Nakamura, and S. Nielsen, Soft Matter (2011).

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

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

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

16 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. 17