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 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|
|Official 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)|
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