Intercellular domain organization

Figure 7 The possible mechanisms involved in the effect of penetration enhancers on the lipid organization of the intercellular domains in the stratum corneum. (A) Intercalation of the enhancer in the lipid lamellae. (B) Phase separation between enhancer and skin lipids in the lamellae. (C) Phase separation between lipid lamellae and an enhancer-rich phase. (D) Intercalation of the enhancer in the lipid lamellae and simultaneous phase separation between lipid lamellae and enhancer. (E) Phase separation within the lamellae and separation between an enahncer-rich phase and the lamellar phase. (F) Disappearance of the lamellar phases.

FIGURE 12.1 Penetration enhancer activity, (a) Action at intercellular lipids. Some of the ways by which penetration enhancers attack and modify the well-organized intercellular lipid domain of the stratum comeum. (b) Action at desmosomes and protein structures. Such dramatic disruption by enhancers (particularly potent solvents) as they split the stratum corneum into additional squames and individual cells would be clinically unacceptable, (c) Action within comeocytes. Swelling, further keratin denaturation and vacuolation within individual horny layer cells would not be so drastic but would usually be cosmetically challenging (see Menon and Lee [69] for further details). (Reproduced from Barry, B.W., Nat. Biotechnol. 22, 165, 2004. With permission.)... 

It is the nature of the stratum corneum, the outermost skin layer, that is responsible for the ability of terrestrial animals to exist in a non-aquatic environment without desiccation. The ability to control both the loss of water and the influx of potentially harmful chemicals and micro-organisms is the result of the evolution of a unique mixture of protein and lipid materials which collectively form this coherent membrane composed of distinct domains. These domains are principally protein, associated with the keratinocytes, and lipid, largely contained within the intercellular spaces. 

GFP [103]. PDZ is a structural domain found in signalling proteins of living organisms and plants (PDZ stands for Post synaptic density protein, Drosophilia disc large mmour suppressor, and Zonula occludens-1) which is a multidomain protein localised at intercellular junctions. Claudin-1 is a human protein which regulates cellular transformation and plays a role in metastatic colon cancer [104]. 

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