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 0006-3495

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Abstract

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
Publisher:	Biophysical Society
ISSN:	0006-3495
Date:	15 November 2008
Volume:	Vol.95
Number:	No.10
Page Range:	pp. 4763-4771
Identification Number:	10.1529/biophysj.108.138545
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Engineering and Physical Sciences Research Council (EPSRC), Unilever (Firm)
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URI:	http://wrap.warwick.ac.uk/id/eprint/40615

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