Simulations of skin barrier function : free energies of hydrophobic and hydrophilic transmembrane pores in ceramide bilayers
Notman, Rebecca, Anwar, Jamshed, Briels, W. J., Noro, Massimo, 1968- and den Otter, W. K.. (2008) Simulations of skin barrier function : free energies of hydrophobic and hydrophilic transmembrane pores in ceramide bilayers. Biophysical Journal, Vol.95 (No.10). pp. 4763-4771. ISSN 0006-3495Full text not available from this repository.
Official URL: http://dx.doi.org/10.1529/biophysj.108.138545
Transmembrane pore formation is central to many biological processes such as ion transport, cell fusion, and viral infection. Furthermore, pore formation in the ceramide bilayers of the stratum corneum may be an important mechanism by which penetration enhancers such as dimethylsulfoxide (DMSO) weaken the barrier function of the skin. We have used the potential of mean constraint force (PMCF) method to calculate the free energy of pore formation in ceramide bilayers in both the innate gel phase and in the DMSO-induced fluidized state. Our simulations show that the fluid phase bilayers form archetypal water-filled hydrophilic pores similar to those observed in phospholipid bilayers. In contrast, the rigid gel-phase bilayers develop hydrophobic pores. At the relatively small pore diameters studied here, the hydrophobic pores are empty rather than filled with bulk water, suggesting that they do not compromise the barrier function of ceramide membranes. A phenomenological analysis suggests that these vapor pores are stable, below a critical radius, because the penalty of creating water-vapor and tail-vapor interfaces is lower than that of directly exposing the strongly hydrophobic tails to water. The PMCF free energy pro. le of the vapor pore supports this analysis. The simulations indicate that high DMSO concentrations drastically impair the barrier function of the skin by strongly reducing the free energy required for pore opening.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Skin absorption, Ceramides, Bilayer lipid membranes, Dimethyl sulfoxide, Molecular dynamics -- Simulation methods|
|Journal or Publication Title:||Biophysical Journal|
|Date:||15 November 2008|
|Page Range:||pp. 4763-4771|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Engineering and Physical Sciences Research Council (EPSRC), Unilever (Firm)|
|References:||1. Cohen, F. S., and G. B. Melikyan. 2004. The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement. J. Membr. Biol. 199:1–14. 2. Cevc, G. 2004. Lipid vesicles and other colloids as drug carriers on the skin. Adv. Drug Deliv. Rev. 56:675–711. 3. Tieleman, D. P. 2006. Computer simulations of transport through membranes: passive diffusion, pores, channels and transporters. Clin. Exp. Pharmacol. Physiol. 33:893–903. 4. Javadov, S., and M. Karmazyn. 2007. Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell. Physiol. Biochem. 20:1–22. 5. Tolpekina, T. V., W. K. den Otter, and W. J. Briels. 2004. Simulations of stable pores in membranes: system size dependence and line tension. J. Chem. Phys. 121:8014–8020. 6. Tolpekina, T. V., W. K. den Otter, and W. J. Briels. 2004. Nucleation free energy of pore formation in an amphiphilic bilayer studied by molecular dynamics simulations. J. Chem. Phys. 121:12060–12066. 7. Wohlert, J., W. K. den Otter, O. Edholm, and W. J. Briels. 2006. Free energy of a trans-membrane pore calculated from atomistic molecular dynamics simulation. J. Chem. Phys. 124:154905. 8. Farago, O., and C. D. Santangelo. 2005. Pore formation in fluctuating membranes. J. Chem. Phys. 122:044901. 9. Evans, E., V. Heinrich, F. Ludwig, and W. Rawicz. 2003. Dynamic tension spectroscopy and strength of biomembranes. Biophys. J. 85:2342–2350. 10. Melikov, K. C., V. A. Frolov, A. Shcherbakov, A. V. Samsonov, and Y. A. Chizmadzhev. 2001. Voltage-induced nonconductive pre-pores and metastable single pores in unmodified planar lipid bilayer. Biophys. J. 80:1829–1836. 11. Loison, C., M. Mareschal, and F. Schmid. 2004. Pores in bilayer membranes of amphiphilic molecules: coarse-grained molecular dynamics simulations compared with simple mesoscopic models. J. Chem. Phys. 121:1890–1900. 12. Tieleman, D. P., H. Leontiadou, A. E. Mark, and S. J. Marrink. 2003. Simulation of pore formation in lipid bilayers by mechanical stress and electric fields. J. Am. Chem. Soc. 125:6382–6383. 13. Wang, Z. J., and D. Frenkel. 2005. Pore nucleation in mechanically stretched bilayer membranes. J. Chem. Phys. 123:154701. 14. Beckstein, O., P. C. Biggin, and M. S. P. Sansom. 2001. A hydrophobic gating mechanism for nanopores. J. Phys. Chem. B. 105: 12902–12905. 15. Beckstein, O., and M. S. P. Sansom. 2006. A hydrophobic gate in an ion channel: the closed state of the nicotinic acetylcholine receptor. Phys. Biol. 3:147–159. 16. Beckstein, O., and M. S. P. Sansom. 2004. The influence of geometry, surface character, and flexibility on the permeation of ions and water through biological pores. Phys. Biol. 1:42–52. 17. Beckstein, O., and M. S. P. Sansom. 2003. Liquid-vapor oscillations of water in hydrophobic nanopores. Proc. Natl. Acad. Sci. USA. 100: 7063–7068. 18. Hauser, J. M. L., B. M. Buehrer, and R. M. Bell. 1994. Role of ceramide in mitogenesis induced by exogenous sphingoid bases. J. Biol. Chem. 269:6803–6809. 19. Perry, D. K., and Y. A. Hannun. 1998. The role of ceramide in cell signaling. Biochim. Biophys. Acta. 1436:233–243. 20. Kronke, M. 1999. Biophysics of ceramide signaling: interaction with proteins and phase transition of membranes. Chem. Phys. Lipids. 101:109–121. 21. Bouwstra, J. A., F. E. R. Dubbelaar, G. S. Gooris, and M. Ponec. 2000. The lipid organization in the skin barrier. Acta Derm. Venereol. 80:23–30. 22. Williams, A. C., and B. W. Barry. 2004. Penetration enhancers. Adv. Drug Deliv. Rev. 56:603–618. 23. Notman, R., W. K. den Otter, M. G. Noro, W. J. Briels, and J. Anwar. 2007. The permeability enhancing mechanism of DMSO in ceramide bilayers simulated by molecular dynamics. Biophys. J. 93: 2056–2068. 24. Notman, R., M. Noro, B. O’Malley, and J. Anwar. 2006. Molecular basis for dimethylsulfoxide (DMSO) action on lipid membranes. J. Am. Chem. Soc. 128:13982–13983. 25. Gurtovenko, A. A., and J. Anwar. 2007. Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide. J. Phys. Chem. B. 111:10453–10460. 26. den Otter, W. K., and W. J. Briels. 1998. The calculation of free-energy differences by constrained molecular-dynamics simulations. J. Chem. Phys. 109:4139–4146. 27. den Otter, W. K. 2000. Thermodynamic integration of the free energy along a reaction coordinate in Cartesian coordinates. J. Chem. Phys. 112:7283–7292. 28. Schlitter, J., and M. Kla¨hn. 2003. A new concise expression for the free energy of a reaction coordinate. J. Chem. Phys. 118:2057–2060. 29. Berger, O., O. Edholm, and F. Jahnig. 1997. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys. J. 72:2002–2013. 30. Bordat, P., J. Sacristan, D. Reith, S. Girard, A. Glattli, and F. Muller- Plathe. 2003. An improved dimethyl sulfoxide force field for molecular dynamics simulations. Chem. Phys. Lett. 374:201–205. 31. Berendsen, H. J. C., J. P. M. Postma, W. F. van Gunsteren, and W. F. Hermans. 1981. Interaction models for water in relation to protein hydration. In Intermolecular Forces. B. Pullman, editor. D. Reidel, Dordrecht, The Netherlands. 32. Lindahl, E., B. Hess, and D. van der Spoel. 2001. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J. Mol. Model. 7:306–317. 33. Litster, J. D. 1975. Stability of lipid bilayers and red blood cell membranes. Phys. Lett. A. 53:193–194. 34. Moldovan, D., D. Pinisetty, and R. V. Devireddy. 2007. Molecular dynamics simulations of pore growth in lipid bilayer membranes in the presence of edge-active agents. Appl. Phys. Lett. 91:204104. 35. Allen, R., J.-P. Hansen, and S. Melchionna. 2003. Molecular dynamics investigation of water permeation through nanopores. J. Chem. Phys. 119:3905–3913. 36. Allen, R., S. Melchionna, and J.-P. Hansen. 2002. Intermittent permeation of cylindrical nanopores by water. Phys. Rev. Lett. 89:175502. 37. Tepper, H. L., and G. A. Voth. 2005. Protons may leak through pure lipid bilayers via a concerted mechanism. Biophys. J. 88:3095–3108. 38. Weast, R. C. (Editor.) 1970. CRC Handbook of Chemistry and Physics. 50 Ed. CRC Press, Cleveland, OH. 39. Jiang, F. Y., Y. Bouret, and J. T. Kindt. 2004. Molecular dynamics simulations of the lipid bilayer edge. Biophys. J. 87:182–192. 40. Evans, E., and F. Ludwig. 2000. Dynamic strengths of molecular anchoring and material cohesion in fluid biomembranes. J. Phys. Condens. Mat. 12:A315–A320. 41. Loi, S., G. Sun, V. Franz, and H.-J. Butt. 2002. Rupture of molecular thin films observed in atomic force microscopy. II. Experiment. Phys. Rev. E. 66:031602. 42. Zhelev, D. V., and D. Needham. 1993. Tension-stabilized pores in giant vesicles: determination of pore size and pore line tension. Biochim. Biophys. Acta. 89:1147–1157. 43. Brochard-Wyart, F., P. G. de Gennes, and O. Sandre. 2000. Transient pores in stretched vesicles: role of leak-out. Physica A. 278: 32–51. 44. Moroz, J. D., and P. Nelson. 1997. Dynamically stabilized pores in bilayer membranes. Biophys. J. 72:2211–2216.|
Actions (login required)