Publication

Simulations of Skin Barrier Function: Free Energies of Hydrophobic and Hydrophilic Transmembrane Pores in Ceramide Bilayers

Anwar, Jamshed
; 
Notman, R.
; 
Noro, M.G.
; 
den Otter, W.K.
; 
Briels, W.J.
Publication Date
2008
End of Embargo
Supervisor
Keywords
Skin Barrier Function, Membrane Pore Formation, Dimethyl Sulfoxide, DMSO, Ceramide Bilayers, Molecular Dynamics Simulations, Free Energies
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Collections
Life Sciences Publications
Show all metadata
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 profile 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.
URI
http://hdl.handle.net/10454/4754
Version
No full-text in the repository
Citation
Notman, R., Anwar, J., Briels, W.J., Noro, M.G. 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.
Link to publisher’s version
Link to published version
Link to Version of Record
https://doi.org/10.1529/biophysj.108.138545
Type
Article
Qualification name
Notes