Molecular models of the intercellular lipid lamellae from epidermal stratum corneum

The purpose of the present study was to test the hypothesis that the 13 nm trilamellar repeat units within the intercellular spaces of epidermal stratum corneum are composed of lamellae with alternating 5-3-5 nm dimensions as presented in previous models [J. Invest. Dermatol. 92 (1989) 251, P.W. Wertz, Integral lipids in hair and stratum corneum, in: P. Jolles, H. Zahn, H. Hocker (Eds.), Hair: Biology And Structure, Birkhauser Verlag, Basel, 1996, pp. 227-238, Acta Derm.-Venereol., Suppl. 208 (2000) 23]. Electron density profiles were measured from transmission electron micrographs of porcine stratum corneum prepared using ruthenium tetroxide [J. Invest. Dermatol. 92 (1989) 251]. Center-to-center distances of adjacent electron-dense bands as well as adjacent lucent bands were measured. Dense band center-to-center measurements were consistent with a 5-3-5 nm arrangement. However, lucent band center-to-center measurements revealed uniform lamellar thickness. It is suggested that linoleate chains in the central lamella reduce more ruthenium than the predominantly saturated chains in the outer lamellae and that this additional reduced ruthenium accumulates under the polar head group regions. A similar phenomenon involving the sphingosine moieties of the covalently bound omega-hydroxyceramide molecules accounts for the three-band pattern seen between the ends of adjacent corneocytes. It is concluded that the component lamellae of the several types of 13 nm trilamellar units of the stratum corneum are all of equal thickness.     

Molecular models of the intercellular lipid lamellae from epidermal stratum corneum

The purpose of the present study was to test the hypothesis that the 13 nm trilamellar repeat units within the intercellular spaces of epidermal stratum corneum are composed of lamellae with alternating 5-3-5 nm dimensions as presented in previous models [J. Invest. Dermatol. 92 (1989) 251, P.W. Wertz, Integral lipids in hair and stratum corneum, in: P. Jolles, H. Zahn, H. Hocker (Eds.), Hair: Biology And Structure, Birkhauser Verlag, Basel, 1996, pp. 227-238, Acta Derm.-Venereol., Suppl. 208 (2000) 23]. Electron density profiles were measured from transmission electron micrographs of porcine stratum corneum prepared using ruthenium tetroxide [J. Invest. Dermatol. 92 (1989) 251]. Center-to-center distances of adjacent electron-dense bands as well as adjacent lucent bands were measured. Dense band center-to-center measurements were consistent with a 5-3-5 nm arrangement. However, lucent band center-to-center measurements revealed uniform lamellar thickness. It is suggested that linoleate chains in the central lamella reduce more ruthenium than the predominantly saturated chains in the outer lamellae and that this additional reduced ruthenium accumulates under the polar head group regions. A similar phenomenon involving the sphingosine moieties of the covalently bound ω-hydroxyceramide molecules accounts for the three-band pattern seen between the ends of adjacent corneocytes. It is concluded that the component lamellae of the several types of 13 nm trilamellar units of the stratum corneum are all of equal thickness.     

Molecular mechanisms of action of different concentrations of ethanol in water on ordered structures of intercellular lipids and soft keratin in the stratum corneum

Ethanol (EtOH) is one of the bases in topically applied medicines that promote the skin permeation of drugs. Although the effects of EtOH have been attributed to structural modifications in the stratum corneum, the underlying mechanisms, especially the influence of different concentrations of EtOH, have not been examined extensively. Structural modifications in the stratum corneum of hairless mouse due to the application of EtOH/water mixture were herein investigated at the molecular level using synchrotron X-ray diffraction. The results revealed that all EtOH concentrations examined greatly modified the short lamellar structures containing the aqueous layer in intercellular lipids and the structure of keratin fibrils in corneocytes, which can take up hydrophilic compounds. However, the long lamellar and the hydrocarbon-chain packing structures were unaffected by EtOH. Changes to the short lamellar structures were not proportional to the concentration of EtOH. However, the keratin fibril structures changed gradually with increasing EtOH concentration. The X-ray diffraction experiments enabled the effects of different EtOH concentrations on the morphology of the stratum corneum to be assessed by using a number of experimental samples to avoid variations due to individual differences. The results indicated that alterations to the short lamellar structures appeared to be related to the skin permeability of drugs with the application of EtOH/water mixture, and monotonous structural changes in the keratin fibrils with an increase in EtOH concentration may contribute to this permeation as supplement. These results will be useful for the development of new drug formulations containing EtOH.     

Molecular dynamics simulations of pore formation dynamics during the rupture process of a phospholipid bilayer caused by high-speed equibiaxial stretching

Rupture of a phospholipid bilayer under mechanical stresses is triggered by pore formation in an intact bilayer. To understand the molecular details of the dynamics of pore formation we perform molecular dynamics simulations of a phospholipid bilayer under two different equibiaxial stretching conditions: first, unsteady stretching with various stretching speeds in the range of 0.1-1.0m/s, and second, quasistatic stretching. We analyze (i) patterns of pore formation, (ii) the critical area where a pore forms, (iii) the deformation of the bilayer, and (iv) the apparent breaking force. With stretching, the bilayer deforms anisotropically due to lipid chain packing and water penetrating into the hydrophilic region of the bilayer, and when the area exceeds a critical value, water filled pore structure penetrating the bilayer forms and develops into a large pore, resulting in rupture. For a high stretching speed, small pores (multipore) can temporarily form in a small area. It has been statistically determined that the probability of the multipore formation, the critical areal strain, and the apparent breaking force increase with the stretching speed in the range of 0-50%, 0.8-2.0, and 250-400 pN, respectively. The results qualitatively agree with the experimental and other simulation results, and rationalize the leakage of hemoglobin from erythrocytes in shock wave experiments.     

Molecular dynamics simulations of C-terminal decapeptide of gastrin-releasing peptide in DMPC bilayers: structure, stability and orientation of the peptide hormone within the bilayers

Gastrin-releasing peptide (GRP) is a member of bombesin-like peptides and bombesin and neuromedin B are other members of this family. They act on receptors that belong to the GPCR superfamily and exert important physiological functions upon binding to their receptors. The biologically active C-terminal decapeptide of GRP (GRP10) was studied in explicit DMPC bilayers using molecular dynamics simulations. In the initial conformation, the peptide was placed perpendicular to the membrane plane and the peptide-membrane complex with approximately 20,000 atoms was simulated for a period of 8 ns. After a 5 ns simulation, GRP10 adopted a tilted orientation and the tilt angle with respect to the bilayer normal was approximately 60 masculine. Analysis of the interactions of individual residues indicated the role of histidine residues in maintaining a tilted orientation.