Molecular Organization of the Lipid Matrix in Stratum Corneum and Its Relevance for the Protective Functions of Human Skin

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Abstract

The extracellular matrix of stratum corneum participates actively in the defensive performance of human skin. The unique lamellar organization of the lipids, resulting from their exceptional composition, ensures the low permeability of the skin for xenobiotics, limits the loss of water from the living tissues, and contributes to the formation of a barrier layer of high mechanical integrity, flexibility, and cohesive strength. Both crystalline and disordered lipid phases exist in the lamellae, but their 3D organization remains to be definitely established. Understanding the correlation between composition, molecular organization, and properties of the lipid matrix helps to elucidate the etymology of skin disorders and diseases and offers the potential to develop new, efficient skin therapies.

Keywords

Stratum Corneum Molecular Organization Lipid Matrix Stratum Corneum Lipid Human Stratum Corneum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Winsor T, Burch GE (1944) Differential roles of layers in human epigastric skin on diffusion rate of water. Arch Intern Med 74:428–435Google Scholar
  2. 2.
    Blank IH (1952) Factors which influence the water content of the stratum corneum. J Invest Dermatol 18:433–440PubMedGoogle Scholar
  3. 3.
    Elias PM (2004) The epidermal permeability barrier: from the early days at Harvard to emerging concepts. J Invest Dermatol 122:xxxvi–xxxixPubMedGoogle Scholar
  4. 4.
    Kligman AM (2006) A brief history of how the dead stratum corneum became alive. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor and Francis, New York, pp 15–24Google Scholar
  5. 5.
    Kligman AM (2011) Corneobiology and corneotherapy – a final chapter. Int J Cosm Sci  33:197–209 Google Scholar
  6. 6.
    Elias PM (2006) Defensive functions of the Stratum corneum: Integrative aspects. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor and Francis, New York, pp 5–14Google Scholar
  7. 7.
    Brody I (1966) Intercellular space in normal human stratum corneum. Nature 209:472–476PubMedGoogle Scholar
  8. 8.
    Harding CR (2004) The stratum corneum: structure and function in health and disease. Dermatol Ther 17:6–15PubMedGoogle Scholar
  9. 9.
    Bouwstra JA, Ponec M (2006) The skin barrier in healthy and diseased state. Biochim Biophys Acta-Biomembranes 1758:2080–2095Google Scholar
  10. 10.
    Elias PM (2005) Stratum corneum defensive functions: an integrated view. J Invest Dermatol 125:183–200PubMedGoogle Scholar
  11. 11.
    Di Nardo A, Gallo RL (2006) Cutaneous barriers in defense against microbial invasion. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor and Francis, New York, pp 363–378Google Scholar
  12. 12.
    Rawlings AV (2006) Sources and role of Stratum corneum hydration. In: Elias PM, Feingold KR (eds) Skin barrier. Taylor and Francis, New York, pp 399–426Google Scholar
  13. 13.
    Nickoloff BJ, Stevens SR (2006) What have we learned in dermatology from the biologic therapies? J Am Acad Dermatol 54:S143–S151PubMedGoogle Scholar
  14. 14.
    Wertz PW, van der Bergh B (1998) The physical, chemical, and functional properties of lipids in the skin and other biological barriers. Chem Phys Lipids 91:85–96Google Scholar
  15. 15.
    Wertz PW, Downing DT (1991) Epidermal lipids. In: Goldsmith LA (ed) Physiology, biochemistry, and molecular biology of the skin. Oxford University Press, Oxford, pp 205–236Google Scholar
  16. 16.
    Feingold KR (2007) The role of epidermal lipids in cutaneous permeability barrier homeostasis. J Lipid Res 48:2531–2546PubMedGoogle Scholar
  17. 17.
    Wertz PW, Swartzendruber DC, Madison KC et al (1987) Composition and morphology of epidermal cyst lipids. J Invest Dermatol 89:419–425PubMedGoogle Scholar
  18. 18.
    Masukawa Y, Narita H, Shimizu E et al (2008) Characterization of overall ceramide species in human stratum corneum. J Lipid Res 49:1466–1476PubMedGoogle Scholar
  19. 19.
    Harding CR, Moore DJ, Rawlings AV (2010) Ceramides and the skin. In: Baran R, Maibach HI (eds) Textbook of cosmetic dermatology. Informa Healthcare, New York, pp 150–164Google Scholar
  20. 20.
    van Smeden J, Hoppel L, van der Heijden R et al (2011) LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery. J Lipid Res 52:1211–1221PubMedGoogle Scholar
  21. 21.
    Motta S, Monti M, Sesana S et al (1993) Ceramide composition of the psoriatic scale. Biochim Biophys Acta 1182:147–151PubMedGoogle Scholar
  22. 22.
    Wertz PW, Madison KC, Downing DT (1989) Covalently bound lipids of human stratum corneum. J Invest Dermatol 92:109–111PubMedGoogle Scholar
  23. 23.
    Hill J, Paslin D, Wertz PW (2006) A new covalently bound ceramide from human stratum corneum – w-hydroxyacylphytosphingosine. Int J Cosmet Sci 28:225–230PubMedGoogle Scholar
  24. 24.
    Wertz PW, Miethke MC, Long SA et al (1985) The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol 84:410–412PubMedGoogle Scholar
  25. 25.
    Dahlén B, Pascher I (1979) Thermotropic phase behaviour of tetracosanoylphytosphingosine. Chem Phys Lipids 24:119–133Google Scholar
  26. 26.
    Kiselev MA, Ryabova NY, Balagurov AM et al (2005) New insights into the structure and hydration of a stratum corneum lipid model membrane by neutron diffraction. Eur Biophys J 34:1030–1040PubMedGoogle Scholar
  27. 27.
    Brief E, Kwak S, Cheng JTJ et al (2009) Phase behavior of an equimolar mixture of N-palmitoyl-d-erythro-sphingosine, cholesterol, and palmitic acid, a mixture with optimized hydrophobic matching. Langmuir 25:7523–7532PubMedGoogle Scholar
  28. 28.
    O’Malley B, Moore DJ, Noro M, et al. (2005) Towards a mechanical model of skin: Insights into Stratum corneum mechanical properties from hierarchical models of lipid organization. Mat Res Soc Symp Proc 844: Y5.7Google Scholar
  29. 29.
    Pascher I (1976) Molecular arrangements in sphingolipids: conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability. Biochim Biophys Acta 455:433–451PubMedGoogle Scholar
  30. 30.
    Rerek ME, Moore DJ (2007) Skin lipid structure: Insight into hydrophobic and hydrophilic driving forces for self-assembly using IR spectroscopy. In: Rhein LD, Schlossman M, O’Lenick A, Somasundran P (eds) Surfactants in personal care products and decorative cosmetics. CRC Press, Boca Raton, Surfactant science series, pp 189–209Google Scholar
  31. 31.
    Mendelsohn R, Rerek ME, Moore DJ (2000) Infrared spectroscopy and microscopic imaging of stratum corneum models and skin. Phys Chem Chem Phys 2:4651–4657Google Scholar
  32. 32.
    Norlén L, Nicander I, Lundsjö A et al (1998) A new HPLC-based method for the quantitative analysis of inner stratum corneum lipids with special reference to the free fatty acid fraction. Arch Dermatol Res 290:508–516PubMedGoogle Scholar
  33. 33.
    Fettiplace R, Haydon DA (1980) Water permeability of lipid membranes. Physiol Rev 60:510–550PubMedGoogle Scholar
  34. 34.
    Wertz PW (1996) Integral lipids in hair and Stratum corneum. In: Jolles P, Zahn H, Hocker H (eds) Hair: Biology and structure. Birkhauser Verlag, Basel, pp 227–238Google Scholar
  35. 35.
    Daly TA, Wang M, Regen SL (2011) The origin of cholesterol’s condensing effect. Langmuir 27:2159–2161Google Scholar
  36. 36.
    de Meyer F, Smit B (2009) Effect of cholesterol on the structure of a phospholipid bilayer. Proc Natl Acad Sci USA 106:3654–3658PubMedGoogle Scholar
  37. 37.
    Maxfield FR, Tabas I (2005) Role of cholesterol and lipid organization in disease. Nature 438:612–621PubMedGoogle Scholar
  38. 38.
    Leathes JB (1925) Croonian lectures on the role of fats in vital phenomena. Lancet 205:853–856Google Scholar
  39. 39.
    Róg T, Pasenkiewicz-Gierula M, Vattulainen I et al (2009) Ordering effects of cholesterol and its analogues. Biochim Biophys Acta 1788:97–121PubMedGoogle Scholar
  40. 40.
    Takahashi H, Sinoda K, Hatta I (1996) Effects of cholesterol on the lamellar and the inverted hexagonal phases of dielaidoylphosphatidylethanolamine. Biochim Biophys Acta 1298:209–216Google Scholar
  41. 41.
    McMullen TPW, McElhaney RN (1995) New aspects of the interaction of cholesterol with DPPC bilayers as revealed by high-sensitivity differential scanning calorimetry. Biochim Biophys Acta 1234:90–98PubMedGoogle Scholar
  42. 42.
    Feingold KR (2009) The outer frontier: the importance of lipid metabolism in the skin. J Lipid Res 50:S417–S422PubMedGoogle Scholar
  43. 43.
    Krahn-Bertil E, Hazane-Puch F, Lassel T et al (2009) Skin moisturization by dermonutrition. In: Rawlings AV, Leyden JJ (eds) Skin moisturization. Informa Healthcare USA, Inc., New York, pp 411–425Google Scholar
  44. 44.
    Martinez RI, Peters A (1971) Membrane-coating granules and membrane modifications in keratinizing epithelia. Am J Anat 130:93–120Google Scholar
  45. 45.
    Lavker RM (1976) Membrane coating granules: the fate of the discharged lamellae. J Ultrastruct Res 55:79–86PubMedGoogle Scholar
  46. 46.
    Elias PM, Goerke J, Friend DS (1977) Mammalian epidermal barrier layer lipids: composition and influence on structure. J Invest Dermatol 69:535–546PubMedGoogle Scholar
  47. 47.
    Madison KC, Swartzendruber DC, Wertz PW et al (1987) Presence of intact intercellular lamellae in the upper layers of the stratum corneum. J Invest Dermatol 88:714–718PubMedGoogle Scholar
  48. 48.
    Bouwstra JA (2009) Lipid organization of the skin barrier. In: Rawlings AV, Leyden JJ (eds) Skin moisturization. Informa Healthcare USA, Ins, New York, pp 17–40Google Scholar
  49. 49.
    van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nature Rev Molec Cell Biol 9:112–124Google Scholar
  50. 50.
    Pilgram GSK, Engelsma-van Pelt AM, Bouwstra JA et al (1999) Electron diffraction provides new information on human stratum corneum lipid organization studied in relation to depth and temperature. J Invest Dermatol 113:403–409PubMedGoogle Scholar
  51. 51.
    Friberg SF, Osborne DW (1985) Small angle X-ray diffraction patterns of stratum corneum and a model structure for its lipids. J Dispers Sci Technol 6:485–495Google Scholar
  52. 52.
    Schroeter A, Kessner D, Kiselev MA et al (2009) Basic nanostructure of stratum corneum lipid matrices based on ceramides [EOS] and [AP]: a neutron diffraction study. Biophys J 97:1104–1114Google Scholar
  53. 53.
    Groen D, Poole D, Gooris GS et al (2011) Is an orthorhombic lateral packing and a proper lamellar organization important for the skin barrier function? Biochim Biophys Acta 1808:1529–1537PubMedGoogle Scholar
  54. 54.
    Swartzendruber DC (1992) Studies of epidermal lipids using electron microscopy. Semin Dermatol 11:157–161PubMedGoogle Scholar
  55. 55.
    Swartzendruber DC, Wertz PW, Kitko DJ et al (1989) Molecular models of the intercellular lipid lamellae in mammalian stratum corneum. J Invest Dermatol 92:251–257PubMedGoogle Scholar
  56. 56.
    Schreiner V, Gooris GS, Pfeiffer S et al (2000) Barrier characteristics of different human skin types investigated with X-ray diffraction, lipid analysis, and electron microscopy imaging. J Invest Dermatol 114:654–660PubMedGoogle Scholar
  57. 57.
    Norlén L (2010) Molecular cryo-electron tomography of skin. Open Derm J 4:46–47Google Scholar
  58. 58.
    Al-Amoudi A, Dubochet J, Norlén L (2005) Nanostructure of the epidermal extracellular space as observed by cryo-electron microscopy of vitreous sections of human skin. J Invest Dermatol 124:764–777PubMedGoogle Scholar
  59. 59.
    Percot A, Lafleur M (2001) Direct observation of domains in model stratum corneum lipid mixtures by Raman microspectroscopy. Biophys J 81:2144–2153PubMedGoogle Scholar
  60. 60.
    Wegener M, Neubert RHH, Rettig W et al (1997) Structure of stratum corneum lipids characterized by FT-Raman spectroscopy and DSC. III. Mixtures of ceramides and cholesterol. Chem Phys Lipids 88:73–82PubMedGoogle Scholar
  61. 61.
    Bommannan D, Potts RO, Guy RH (1990) Examination of stratum corneum barrier function in vivo by infrared spectroscopy. J Invest Dermatol 95:403–408PubMedGoogle Scholar
  62. 62.
    Babita K, Kumar V, Rana V et al (2006) Thermotropic and spectroscopic behavior of skin: relationship with percutaneous permeation enhancement. Curr Drug Deliv 3:95–113PubMedGoogle Scholar
  63. 63.
    Mendelsohn R, Flach CR, Moore DJ (2006) Determination of molecular conformation and permeation in skin via IR spectroscopy, microscopy, and imaging. Biochim Biophys Acta 1758:923–933PubMedGoogle Scholar
  64. 64.
    Boncheva M, Damien F, Normand V (2008) Molecular organization of the lipid matrix in intact stratum corneum using ATR-FTIR spectroscopy. Biochim Biophys Acta 1778:1344–1355PubMedGoogle Scholar
  65. 65.
    Kitson N, Thewalt J, Lafleur M et al (1994) A model membrane approach to the epidermal permeability barrier. Biochemistry 33:6707–6715PubMedGoogle Scholar
  66. 66.
    Rehfeld SJ, Plachy WZ, Williams ML et al (1988) Calorimetric and electron spin resonance examination of lipid phase transitions in human stratum corneum: molecular basis for normal cohesion and abnormal desquamation in recessive X-linked ichthyosis. J Invest Dermatol 91:499–505PubMedGoogle Scholar
  67. 67.
    Queiros MP, Sousa Neto D, Alonso A (2005) Dynamics and partitioning of spin-labelled stearates into the lipid domain of stratum corneum. J Control Release 106:374–385PubMedGoogle Scholar
  68. 68.
    Norlén L, Placsencia I, Bagatolli LA (2008) Stratum corneum lipid organization as observed by atomic force microscopy, confocal and two-photon excitation fluorescence microscopy. Int J Cosmet Sci 30:391–411PubMedGoogle Scholar
  69. 69.
    Norlén L, Plasencia Gil I, Simonsen A et al (2007) Human stratum corneum lipid organization as observed by atomic force microscopy of Langmuir-Blodgett films. J Struct Biol 158:386–400PubMedGoogle Scholar
  70. 70.
    Lafleur M (1998) Phase behaviour of model stratum corneum lipid mixtures: an infrared spectroscopy investigation. Can J Chem 76:1501–1511Google Scholar
  71. 71.
    Moore DJ, Rerek ME, Mendelsohn R (1997) FTIR spectroscopy studies of the conformational order and phase behavior of ceramides. J Phys Chem B 101:8933–8940Google Scholar
  72. 72.
    Moore DJ, Rerek ME (2000) Insight into the molecular organization of lipids in the skin barrier from infrared spectroscopy studies of stratum corneum lipid models. Acta Derm Venereol Supp 208:16–22Google Scholar
  73. 73.
    Bouwstra JA, Gooris GS, Ponec M (2002) The lipid organization of the skin barrier: liquid and crystalline domains coexist in lamellar phases. J Biol Phys 28:211–223Google Scholar
  74. 74.
    Bouwstra JA, de Graaff A, Gooris GS et al (2003) Water distribution and related morphology in human stratum corneum at different hydration levels. J Invest Dermatol 120:750–758PubMedGoogle Scholar
  75. 75.
    Pensack RD, Michniak BB, Moore DJ et al (2006) Infrared kinetic/structural studies of barrier reformation in intact stratum corneum following thermal perturbation. Appl Spectrosc 60:1399–1404PubMedGoogle Scholar
  76. 76.
    Damien F, Boncheva M (2010) The extent of orthorhombic lipid phases in the stratum corneum determines the barrier efficiency of human skin in vivo. J Invest Dermatol 130:611–614PubMedGoogle Scholar
  77. 77.
    Gennis RB (1989) Biomembranes: molecular structure and function. Springer-Verlag Inc., NYGoogle Scholar
  78. 78.
    Mukherjee S, Maxfield FR (2000) Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic 1:203–211PubMedGoogle Scholar
  79. 79.
    Nicolaides N (1974) Skin lipids: their biochemical uniqueness. Science 186:19–26PubMedGoogle Scholar
  80. 80.
    Yagi E, Sakamoto K, Nakagawa K (2006) Depth dependence of stratum corneum lipid ordering: a slow-tumbling simulation for electron paramagnetic resonance. J Invest Dermatol 127:895–899PubMedGoogle Scholar
  81. 81.
    Madison KC (2003) Barrier function of the skin: “La raison d’être” of the epidermis. J Invest Dermatol 121:231–241PubMedGoogle Scholar
  82. 82.
    Janssens M, Gooris GS, Bouwstra JA (2009) Infrared spectroscopy studies of mixtures prepared with synthetic ceramides varying in head group architecture: coexistence of liquid and crystalline phases. Biochim Biophys Acta 1788:732–742PubMedGoogle Scholar
  83. 83.
    Garson J-C, Doucet J, Lévêque J-L et al (1991) Oriented structures in human stratum corneum revealed by X-ray diffraction. J Invest Dermatol 96:43–49PubMedGoogle Scholar
  84. 84.
    Bouwstra JA, Gooris GS, Salomons-de Vries JA et al (1992) Structure of stratum corneum as a function of temperature and hydration: a wide-angle X-ray diffraction study. Int J Pharm 84:205–216Google Scholar
  85. 85.
    Bouwstra JA, Gooris GS, Dubbelaar FER et al (2002) Phase behavior of stratum corneum lipid mixtures based on human ceramides: the role of natural and synthetic ceramide 1. J Invest Dermatol 118:606–617PubMedGoogle Scholar
  86. 86.
    Sousa Neto D, Gooris GS, Bouwstra JA (2011) Effect of w-acylceramides on the lipid organization of stratum corneum model membranes evaluated by X-ray diffraction and FTIR studies (Part I). Chem Phys Lipids 164:184–195PubMedGoogle Scholar
  87. 87.
    Bouwstra JA, Gooris GS (2010) The lipid organization in human stratum corneum and model systems. Open Derm J 4:10–13Google Scholar
  88. 88.
    Caussin J, Gooris GS, Janssens M et al (2008) Lipid organization in human and porcine stratum corneum differs widely, while lipid mixtures with porcine ceramides model human stratum corneum lipid organization very closely. Biochim Biophys Acta 1778:1472–1482PubMedGoogle Scholar
  89. 89.
    Hill JR, Wertz PW (2003) Molecular models of the intercellular lamellae from epidermal stratum corneum. Biochim Biophys Acta 1616:121–126PubMedGoogle Scholar
  90. 90.
    Forslind B (1994) A domain mosaic model of the skin barrier. Acta Derm Venereol 74:1–6PubMedGoogle Scholar
  91. 91.
    Forslind B, Engstrom S, Engblom J et al (1997) A novel approach to the understanding of human skin barrier function. J Dermatol Sci 14:115–125PubMedGoogle Scholar
  92. 92.
    Potts RO, Francoeur ML (1991) The influence of stratum corneum morphology on water permeability. J Invest Dermatol 96:495–499PubMedGoogle Scholar
  93. 93.
    Kitson N, Thewalt JL (2000) Hypothesis: the epidermal permeability barrier is a porous medium. Acta Derm Venereol Supp 208:12–15Google Scholar
  94. 94.
    Bouwstra JA, Dubbelaar FER, Gooris GS et al (2000) The lipid organization in the skin barrier. Arch Dermatol Res Supp 208:23–30Google Scholar
  95. 95.
    McIntosh TJ (2003) Organization of skin stratum corneum extracellular lipid lamellae: diffraction evidence for asymmetric distribution of cholesterol. Biophys J 85:1675–1681PubMedGoogle Scholar
  96. 96.
    Norlén L (2001) Skin barrier structure and function: the single gel phase model. J Invest Dermatol 117:830–836PubMedGoogle Scholar
  97. 97.
    Kiselev MA (2007) Conformation of ceramide 6 molecules and chain-flip transitions in the lipid matrix of the outmost layer of mammalian skin, the stratum corneum. Crystallogr Rep 52:525–528Google Scholar
  98. 98.
    McIntosh TJ, Stewart ME, Downing DT (1996) X-ray diffraction analysis of isolated skin lipids: reconstitution of intercellular lipid domains. Bioc­hemistry 35:3649–3653PubMedGoogle Scholar
  99. 99.
    Groen D, Gooris GS, Barlow DJ et al (2011) Disposition of ceramide in model lipid membranes determined by neutron diffraction. Biophys J 100:1481–1489PubMedGoogle Scholar
  100. 100.
    Kessner D, Kiselev MA, Dante S et al (2008) Arrangement of ceramide [EOS] in a stratum corneum lipid model matrix: new aspects revealed by neutron diffraction studies. Eur Biophys J 37:989–999PubMedGoogle Scholar
  101. 101.
    Schroeter A, Kiselev MA, Hauss T et al (2009) Evidence of free fatty acid interdigitation in stratum corneum model membranes based on ceramide [AP] by deuterium labeling. Biochim Biophys Acta 1788:2194–2203PubMedGoogle Scholar
  102. 102.
    Menon GK (2002) New insights into skin structure: scratching the surface. Adv Drug Deliv Rev 54(suppl 1):S3–S17PubMedGoogle Scholar
  103. 103.
    Roelandt T, Giddelo C, Heughebaert C et al (2009) The “caveolae brake hypothesis” and the epidermal barrier. J Invest Dermatol 129:927–936PubMedGoogle Scholar
  104. 104.
    Menon GK, Ghadially R, Williams ML et al (1992) Lamellar bodies as delivery systems of hydrolytic enzymes: implications for normal and abnormal desquamation. Br J Dermatol 126:337–345PubMedGoogle Scholar
  105. 105.
    Rawlings AV, Matts PJ (2005) Stratum corneum moisturization at the molecular level: an update in relation to the dry skin cycle. J Invest Dermatol 124:1099–1110PubMedGoogle Scholar
  106. 106.
    Hachem J-P, Houben E, Crumrine D et al (2006) Serine protease signaling of epidermal permeability barrier homeostasis. J Invest Dermatol 126:2074–2086PubMedGoogle Scholar
  107. 107.
    Voegeli R, Rawlings AV, Doppler S et al (2007) Profiling of serine protease activities in human stratum corneum and detection of a stratum corneum tryptase-like enzyme. Int J Cosmet Sci 29:191–200PubMedGoogle Scholar
  108. 108.
    Grubauer G, Elias PM, Feingold KR (1989) Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 30:323–333PubMedGoogle Scholar
  109. 109.
    Feingold KR, Schmuth M, Elias PM (2007) The regulation of permeability barrier homeostasis. J Invest Dermatol 127:1574–1576PubMedGoogle Scholar
  110. 110.
    Landmann L (1986) Epidermal permeability barrier: transformation of lamellar granule-disks into intercellular sheets by a membrane-fusion process, a freeze-fracture study. J Invest Dermatol 87:202–209PubMedGoogle Scholar
  111. 111.
    Haftek M, Teillon M-H, Schmitt D (1998) Stratum corneum, corneodesmosomes and ex vivo percutaneous penetration. Microsc Res Tech 43:242–249PubMedGoogle Scholar
  112. 112.
    Loefgren H, Pascher I (1977) Molecular arrangement of sphingolipids: the monolayer approach. Chem Phys Lipids 20:273–284Google Scholar
  113. 113.
    Whitesides GM, Mathias JP, Seto CT (1991) Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science 254:1312–1319PubMedGoogle Scholar
  114. 114.
    Atkins PW (1997) Physical Chemistry. Oxford University Press, Oxford, UKGoogle Scholar
  115. 115.
    Bishop KJM, Wilmer CE, Soh S et al (2009) Nanoscale forces and their uses in self-assembly. Small 5:1600–1630PubMedGoogle Scholar
  116. 116.
    Norlén L (2002) Does the single gel phase exist in stratum corneum? J Invest Dermatol 118:899–901Google Scholar
  117. 117.
    Whitesides GM, Grzybowski B (2002) Self-assembly at all scales. Science 295:2418–2421PubMedGoogle Scholar
  118. 118.
    Grzybowski BA, Wilmer CE, Kim J et al (2006) Self-assembly: from crystals to cells. Soft Matter 5:1110–1128Google Scholar
  119. 119.
    Williams ML, Elias PM (1987) The extracellular matrix of stratum corneum: role of lipids in normal and pathological function. CRC Crit Rev Therap Drug Carrier Syst 3:95–122Google Scholar
  120. 120.
    Mitragotri S, Anissimov YG, Bunge AL et al (2011) Mathematical models of skin permeability: an overview. Int J Pharm  418:115–129 Google Scholar
  121. 121.
    Bunge AL, Cleek RL (1995) A new method for estimating dermal absorption from chemical exposure. 2. Effect of molecular weight and octanol-water partitioning. Pharm Res 12:88–95PubMedGoogle Scholar
  122. 122.
    Guy RH (2010) Predicting the rate and extent of fragrance chemical absorption into and through the skin. Chem Res Toxicol 23:864–870PubMedGoogle Scholar
  123. 123.
    Mitragotri S (2003) Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways. J Control Release 86:69–92PubMedGoogle Scholar
  124. 124.
    Levin J, Maibach HI (2005) The correlation between transepidermal water loss and percutaneous absorption: an overview. J Control Release 103:291–299PubMedGoogle Scholar
  125. 125.
    Golden GM, McKie JE, Potts RO (1987) Role of stratum corneum lipid fluidity in transdermal drug flux. J Pharm Sci 76:25–28PubMedGoogle Scholar
  126. 126.
    Golden GM, Guzek DB, Kennedy AH et al (1987) Stratum corneum phase transitions and water barrier properties. Biochemistry 26:2382–2388PubMedGoogle Scholar
  127. 127.
    Potts RO, Francoeur ML (1990) Lipid biophysics of water loss through the skin. Proc Natl Acad Sci USA 87:3871–3873PubMedGoogle Scholar
  128. 128.
    Potts RO, Mak VHW, Guy RH et al (1991) Strategies to enhance permeability via stratum corneum lipid pathways. Adv Lipid Res 24:173–210PubMedGoogle Scholar
  129. 129.
    Naik A, Guy RH (1997) Infrared spectroscopic and differential scanning calorimetric investigations of the Stratum corneum barrier function. In: Potts RO, Guy RH (eds) Mechanisms of transdermal drug delivery. Marcel Dekker, NY, pp 87–162Google Scholar
  130. 130.
    Naik A, Kalia YN, Pirot F et al (1999) Characterization of molecular transport across human Stratum corneum in vivo. In: Bronaugh RL, Maibach HI (eds) Percutaneous adsorption. Marcel Dekker, Inc., NY, pp 149–175Google Scholar
  131. 131.
    Imhof RE, Xiao P, De Jesus MEP et al (2009) New developments in skin barrier measurements. In: Rawlings AV, Leyden JJ (eds) Skin moisturization. Informa Healthcare USA, Inc., New York, pp 463–479Google Scholar
  132. 132.
    de Jaeger M, Groenink W, Bielsa i Guivernau R et al (2006) A novel in vitro percutaneous penetration model: evaluation of barrier properties with p-aminobenzoic acid and two of its derivatives. Pharm Res 23:951–960Google Scholar
  133. 133.
    Pilgram GSK, Vissers DCJ, van der Meulen H et al (2001) Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis. J Invest Dermatol 117:710–717PubMedGoogle Scholar
  134. 134.
    Bouwstra JA, Gooris GS, Dubbelaar FER et al (1999) Cholesterol sulfate and calcium affect stratum corneum lipid organization over a wide temperature range. J Lipid Res 40:2303–2312PubMedGoogle Scholar
  135. 135.
    Milstone LM (2004) Epidermal desquamation. J Dermatol Sci 36:131–140PubMedGoogle Scholar
  136. 136.
    Harding CR, Watkinson AC, Rawlings AV et al (2000) Dry skin, moisturization and corneodesmolysis. Int J Cosm Sci 22:21–52Google Scholar
  137. 137.
    Fluhr JW, Elias PM (2002) Stratum corneum pH: formation and function of the ‘acid mantle’. Exogenous Dermatol 1:163–175Google Scholar
  138. 138.
    Fluhr JW, Kao JS, Jain M et al (2001) Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity. J Invest Dermatol 117:44–51PubMedGoogle Scholar
  139. 139.
    Hachem J-P, Crumrine D, Fluhr J et al (2003) pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. J Invest Dermatol 121:345–353PubMedGoogle Scholar
  140. 140.
    Rawlings AV, Harding CR, Watkinson AC et al (2002) Dry and xerotic skin conditions. In: Leyden JJ, Rawlings AV (eds) Skin moisturization. Marcel Dekker, Inc., New York, N.Y, pp 119–143Google Scholar
  141. 141.
    Hachem J-P, Man M-Q, Crumrine D et al (2005) Sustained serine protease activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol 125:510–520PubMedGoogle Scholar
  142. 142.
    Arseneault M, Lafleur M (2007) Cholesterol-sulfate and Ca2+ modulate the mixing properties of lipids in stratum corneum model mixtures. Biophys J 92:99–114PubMedGoogle Scholar
  143. 143.
    Epstein EHJ, Williams ML, Elias PM (1981) Steroid sulfatase, X-linked ichthyosis and stratum corneum cell cohesion. Arch Dermatol 117:761–763PubMedGoogle Scholar
  144. 144.
    Wu KS, van Osdol WW, Dauskardt RH (2006) Mechanical properties of human stratum corneum: effects of temperature, hydration, and chemical treatment. Biomaterials 27:785–795PubMedGoogle Scholar
  145. 145.
    Berthaud F, Boncheva M (2011) Correlation between the properties of the lipid matrix and the degrees of integrity and cohesion in healthy human stratum corneum. Exper Dermatol 20:255–262Google Scholar
  146. 146.
    Brandner JM, Haftek M, Niessen CM (2010) Adherens junctions, desmosomes and tight junctions in epidermal barrier function. Open Derm J 4:14–20Google Scholar
  147. 147.
    Elias PM (2008) Skin barrier function. Curr Alergy Asthma Rep 8:299–305Google Scholar
  148. 148.
    Elias PM (2010) Therapeutic implications of a barrier-based pathogenesis of atopic dermatitis. Ann Dermatol 22:245–254PubMedGoogle Scholar
  149. 149.
    Prausnitz MR, Mitragotri S, Langer R (2004) Current status and future potential of transdermal drug delivery. Nature Rev Drug Disc 3:115–124Google Scholar
  150. 150.
    Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nature Biotech 26:1261–1268Google Scholar
  151. 151.
    Loden M, Anderson A-C (1996) Effect of topically applied lipids on surfactant-irritated skin. Br J Dermatol 134:215–220PubMedGoogle Scholar
  152. 152.
    Darmstadt GL, Mao-Qiang M, Chi E et al (2002) Impact of topical oils on the skin barrier: possible implications for neonathal health in developing countries. Acta Paediatr 91:546–554PubMedGoogle Scholar
  153. 153.
    Menon GK, Duggan M (2006) Strategies for improving the skin barrier by cosmetic skin care treatments. In: Wille JJ (ed) Skin delivery systems: Transdermals, dermatologicals, and cosmetic actives. Blackwell Publishing, Ames, pp 25–42Google Scholar
  154. 154.
    Jelenco C 3rd, McKinley JC (1976) Studies in burns: XV. Use of a topical lipid in treating human burns. Am Surg 42:838–848Google Scholar
  155. 155.
    Lavrijsen AP, Bouwstra JA, Gooris GS et al (1995) Reduced skin barrier function parallels abnormal stratum corneum lipid organization in patients with lamellar ichthyosis. J Invest Dermatol 105:619–624PubMedGoogle Scholar
  156. 156.
    Rawlings AV, Harding CR (2004) Moisturization and skin barrier function. Dermatol Ther 17(suppl 1):43–48PubMedGoogle Scholar
  157. 157.
    Wiechers JW, Dederen JC, Rawlings AV (2009) Moisturization mechanisms: Internal occlusion by orthorhombic lipid phase stabilizers–a novel mechanism of action of skin moisturization. In: Rawlings AV, Leyden JJ (eds) skin moisturization. Informa Healthcare USA, Inc., New York, pp 309–321Google Scholar
  158. 158.
    Caussin J, Gooris GS, Groenink W et al (2007) Interaction of lipophilic moisturizers on stratum corneum domains in vitro and in vivo. Skin Pharmacol Physiol 20:175–186PubMedGoogle Scholar
  159. 159.
    Caussin J, Rozema E, Gooris GS et al (2009) Hydrophilic and lipophilic moisturizers have similar penetration profiles but different effects on SC water distribution in vivo. Exper Dermatol 18:954–961Google Scholar
  160. 160.
    Caussin J, Gooris GS, Bouwstra JA (2008) FTIR studies show lipophilic moisturizers to interact with stratum corneum lipids, rendering them more densely packed. Biochim Biophys Acta 1778:1517–1524PubMedGoogle Scholar
  161. 161.
    Hadgraft J, Finnin BC (2006) Fundamentals of retarding penetration. In: Smith EW, Maibach HI (eds) Percutaneous penetration enhancers. Taylor and Francis, Boca Raton, pp 361–371Google Scholar
  162. 162.
    Hadgraft J, Peck J, Williams DG et al (1996) Mechanisms of reaction of skin penetration enhancers/retardants: azone and analogues. Int J Pharm 141:17–25Google Scholar
  163. 163.
    Peck JV, Minaskanian G, Hadgraft J (2000) Topical compositions useful as skin penetration retardants. US patent 6,086,905Google Scholar
  164. 164.
    Kaushik D, Batheja P, Kilfoyle B et al (2008) Percutaneous penetration modifiers: enhancement versus retardation. Expert Opin Drug Deliv 5:517–529PubMedGoogle Scholar
  165. 165.
    Kim N, El-Khalili M, Henary MM et al (1999) Percutaneous penetration enhancement activity of aromatic S, S-dimethyliminosulfuranes. Int J Pharm 187:219–229PubMedGoogle Scholar
  166. 166.
    Brain KR, Watkinson AC, Walters KA (1999) Reduction of the skin penetration of xenobiotics using chemical penetration retarders. In: Sohns T, Voicu VA (eds) NBC risks: Current capabilities and future perspectives for protection, NATO Science Series: Disarmament Technologies. Kluwer Academic Publishers, Dordrecht, pp 271–277Google Scholar
  167. 167.
    Li N, Su Q, Tan F et al (2010) Effect of 1,4-cyclohexanediol on percutaneous absorption and penetration of azelaic acid. Int J Pharm 387:167–171PubMedGoogle Scholar
  168. 168.
    Braue EH Jr, Doxzon BF, Lumpkin HL et al (2006) Military perspectives in chemical penetration retardation. In: Smith EW, Maibach HI (eds) Percutaneous penetration enhancers. Taylor and Francis, Boca Raton, pp 385–398Google Scholar
  169. 169.
    Smith EW, Maibach HI (eds) (2006) Percutaneous penetration enhancers. Taylor and Francis, Boca RatonGoogle Scholar
  170. 170.
    Mitragotri S (2000) Synergistic effects of enhancers for transdermal drug delivery. Pharm Res 17:1354–1359PubMedGoogle Scholar
  171. 171.
    Karande P, Jain A, Ergun K et al (2005) Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci USA 102:4688–4693PubMedGoogle Scholar
  172. 172.
    Whitesides GM (1995) Self-assembling materials. Sci Am 273:146–149Google Scholar
  173. 173.
    Lehn J-M (2004) Supramolecular chemistry: from molecular information towards self-organization and complex matter. Rep Prog Phys 67:249–265Google Scholar
  174. 174.
    Lampe MA, Burlingame AL, Whitney J et al (1983) Human stratum corneum lipids: characterization and regional variations. J Lipid Res 24:120–130PubMedGoogle Scholar
  175. 175.
    Gunathilake R, Schurer N, Shoo BA et al (2009) pH-regulated mechanisms account for pigment-type differences in epidermal barrier function. J Invest Dermatol 129:1719–1729PubMedGoogle Scholar
  176. 176.
    Meidan VM, Roper CS (2008) Inter- and intra-individual variability in human skin barrier function: a large scale retrospective study. Toxicol In Vitro 22:1062–1069PubMedGoogle Scholar
  177. 177.
    Moore DJ, Snyder RG, Rerek ME et al (2006) Kinetics of membrane raft formation: fatty acid domains in stratum corneum lipid models. J Phys Chem B 110:2378–2386PubMedGoogle Scholar
  178. 178.
    Boelsma E, Hendriks HFJ, Roza L (2001) Nutritional skin care: health effects of micronutrients and fatty acids. Am J Clin Nutr 73:853–864PubMedGoogle Scholar
  179. 179.
    McDaniel JC, Beluri M, Ahijevych K et al (2008) Omega-3 fatty acids effect on wound healing. Wound Rep Reg 16:337–345Google Scholar
  180. 180.
    Munro S (2003) Lipid rafts: elusive or illusive? Cell 115:377–388PubMedGoogle Scholar
  181. 181.
    Lingwood D, SImons K (2010) Lipid rafts as membrane-organizing principle. Science 327:46–50PubMedGoogle Scholar
  182. 182.
    Dietrich C, Bagatolli LA, Volovyk ZN et al (2001) Lipid rafts reconstituted in model membranes. Biophys J 80:1417–1428PubMedGoogle Scholar
  183. 183.
    London M, London E (2004) Ceramide selectively displaces cholesterol from ordered lipid domains (rafts): Implications for lipid raft structure and function. J Biol Chem 279:9997–10004PubMedGoogle Scholar
  184. 184.
    Boncheva M, Whitesides GM (2005) Making things by self-assembly. MRS Bull 30:736–742Google Scholar
  185. 185.
    Alivisatos AP, Barbara PF, Castelman AW et al (1998) From molecules to materials: current trends and future directions. Adv Mater 10:1297–1336Google Scholar
  186. 186.
    Boncheva M, Whitesides GM (2004) The biomimetic approach to the design of functional self-assembling systems. In: Schwarz JA, Contescu CI, Putyera K (eds) Dekker encyclopedia of nanoscience and nanotechnology, vol 1. CRC Press, Boca Raton, pp 287–294Google Scholar
  187. 187.
    Schaefer-Korting M, Mehnert W, Korting H-C (2007) Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev 59:427–443Google Scholar
  188. 188.
    Mueller RH, Petersen RD, Hommoss A et al (2007) Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev 59:522–530Google Scholar
  189. 189.
    Castner DG, Ratner BD (2002) Biomedical surface science: foundations to frontiers. Surf Sci 500:28–60Google Scholar
  190. 190.
    Martin P (1997) Wound healing – aiming for perfect skin regeneration. Science 276:75–81PubMedGoogle Scholar
  191. 191.
    Ball P (2002) Natural strategies for the molecular engineer. Nanotechnology 13:R15–R28Google Scholar
  192. 192.
    Noireaux V, Maeda YT, Libchaber A (2011) Development of an artificial cell, from self-organization to computation and self-reproduction. Proc Natl Acad Sci USA 108:3473–3480PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Corporate R&D DivisionFirmenich SAGenevaSwitzerland

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