Biophysical Factors in Drug Action 25 



lipophilic aggregates which have a somewhat fibrous appearance 

 and are generally radially disposed across the epicuticle frame- 

 work. The network is interlaced with more hydrated processes 

 from the underlying endocuticle. Lamellation cannot be seen 

 in the epicuticle although it is marked in the endocuticle. This 

 may be due to the more heavily staining outer layer, and as both 

 layers are secreted by the same layer of epidermal cells, it is 

 probable that a lamellar fabric exists also in the epicuticle. The 

 spacing between the layers is relatively wide in the endocuticle 

 and it is possible that a more minute form of structure may be 

 revealed by X-ray diffraction analysis. If we assume the exist- 

 ence of a microscopic lamellar fabric in the epicuticle, and sup- 

 pose that the visible mosaic network is incorporated in the 

 membrane, the gross relationships of the structural components 

 become more apparent (figure 4a). 



99 



Effect of Permeability on "Tanning 



We can explain the action of fat solvents in increasing the 

 permeability of the cuticle to other fat solvents such as ethyl 

 alcohol, by assuming that the solvents swell the more lipophilic 

 radially disposed strands of the mosaic network which extends 

 across the epicuticle. But we still have to account for the asso- 

 ciated increase in the permeability to water, and this makes it 

 necessary to depart somewhat from the usual classical concepts 

 in which the heterogeneity in a membrane is supposed to consist 

 of pores or channels. Any increase in the permeability of the 

 cuticle to water will probably involve the displacement of protec- 

 tive lipid from the more hydrated protein or lipoprotein struc- 

 tures. But if we "tan" the cuticle by"" means of a protein reagent 

 such as />-benzoquinone, the protected protein zones will tan 

 more slowly than those in which access of /'-benzoquinone is 

 restricted by the competitive action of the lipid for the amino 

 groups of the protein. 



As with ethyl alcohol, the access of /'-benzoquinone through 

 the cuticle takes place more rapidly in kerosene than in alcohol 

 or water, and this can be measured by the darkening of the 



