1. The Structure of Phosphor Lipid Membranes Embedded with n-Alcohols Investigated by SAXS and MD-Simulations Ulf Rørbæk Pedersen (RUC) Supervisors Dorthe Posselt (RUC) Peter Westh (RUC) Güenter Peters (DTU)

2. Introduction Method: ● Small angle x-ray scattering (SAXS) ● Molecular Dynamics Simulations (MD-simulations) System: DMPC/hexanol (MD-simulations) and similar systems (SAXS)

3. SAXS Model Smearing from line shaped beam in Kratky camera ( ) q = |k in - k out |

4. SAXS data DMPC/hexan ol DMPC DMPC/hexanol elektron dencity [a.u.]

5. SAXS data

6. Molecular Dynamic Simulations Program: NAMD Force Field: CHARMM27 with modified charges in headgroup, RHF 6-31G*. TIP3 water Constant NPT, P=1 atm (Nosé-Hoover Langevin piston) Periodic boundary conditions Full electrostatics (Particle Mesh Ewald) Time step: 1 fs (velocity Verlet integration method)

7. Membrane area A=59.6 Ų (30˚C)

8. Density profile

9. Voronoi Volumes number carbon in acyl chain mean voronoi volume [ų] V DMPC =1101 ų

10. Order parameter carbon number in acyl chain

11. Flip-flop event  t = 0.4 ns

12. Summary Alcohol molecules intercalate with the hydroxy group in the hydrophilic part and the acyl chain parallel to the fatty acids n-hexanol in a membrane introduces ● a reduction of the thickness (SAXS) ● a condensations of the area (MD) ● a softer membrane (MD) ● more free volume in inner part of membrane (MD) ● more order in outer part of membrane (MD) ● less order in inner part of membrane (MD)

13. Perspectives ● How can we modify the properties of a membrane by doping? ● Permeability ● Concentration dependence ● The dependence of alcohol length ● Other doping molecules (cholesterol, other anesthesia) ● MD-Pulling experiment

14. Equations

15. SAXS of MLV

16. Distribution of Voronoi Volumes

17. Density profile

18. Literature