Biophysical Factors in Drug Action \7 



oily liquid of low dielectric constant. CoUander ^' ^ was in gen- 

 eral agreement with the view that the penetration of nonelectro- 

 lytes through the plasma membrane takes place through the 

 membrane lipids, but he found that small molecules penetrate 

 into the cells of the alga Chara fragilis more rapidly than would 

 be expected from considerations of oil solubility alone. He 

 concluded that the cell membrane acts as a molecular sieve in 

 which the specialized channels become a dominant factor in 

 drug access when the molecular size of the penetrating molecules 

 decreases to a critical value. Nathansohn ^^ was similarly led 

 to conclude that the cell membrane is heterogeneous, but his 

 concept differed from that of CoUander in assuming that the 

 specially differentiated patches are much larger than molecular 

 sieves, and that the penetration of substances depends on their 

 chemical properties rather than on their molecular size. If we 

 accept the view that the cell membrane is heterogeneous and 

 consists of a mosaic arrangement of relatively hydrated patches 

 distributed in a lipophilic framework, we must also suppose that 

 interfaces exist in the membrane structure, which may, however, 

 approximate to a homogeneous lipid layer in certain types of 

 cells. In this way, some measure of agreement is found which 

 relates the Overton-Meyer and Traube principles in terms of 

 structural membrane relationships, rather than the relationships 

 which exist in model systems. 



Investigations on the Erythrocyte Envelope 



The erythrocyte has been the favored object of much investiga- 

 tion. Despite the convergent attack which has been made on 

 the nature of the structural organization of the erythrocyte 

 envelope, a considerable degree of uncertainty still exists as to 

 its precise structure. Here, also, the biological complexities in 

 the system are so marked that many new concepts of cell struc- 

 ture have been based on analogy with simple models. For ex- 

 ample, by means of the analytical leptoscope, Waugh and 

 Schmitt ^^ have estimated that the total thickness of the erythro- 

 cyte envelope is about 200 A. of which up to 100 A. may consist 



