THEORIES OF MEMBRANE PERMEABILITY 129 



than chloroform, hence the volume of liquid below the membrane is con- 

 stantly increasing, and the layer of water rises. In the second test tube the 

 chloroform diffuses through the water membrane more rapidly than the xylene, 

 hence the position of the layer of water is lowered. This behavior is in ac- 

 cordance with the known solubilities of these three compounds in water; ether 

 is the most soluble, chloroform next, and xylene the least. Evidently in this 

 experiment permeability of the water membrane to these three compounds is 

 directly correlated with their solubility in water. 



The most familiar form of the solubility theory as applied to cytoplasmic 

 membranes is the "lipoid solubility" theory first proposed by Overton (1904). 

 In brief this theory holds that substances soluble in lipoids pass readily through 

 the cytoplasmic membranes while others do not. The term "lipoid" is used 

 in a loose way to refer to fats and fat-like compounds. In recent usage the 

 term "lipid" has been rather generally substituted for "lipoid" (Chap. 

 XXIII). Several lines of evidence appear to favor this theory. Among these 

 are: (i) the non-miscibility of protoplasm with water, which probably indi- 

 cates the presence of a film of fatty material on the outer surface of the 

 protoplasm, (2) the fact that most lipoids lower surface tension, and hence 

 theoretically would accumulate at interfaces, and (3) the high resistance 

 of protoplasm to the passage of an electrical current, which indicates that it 

 contains layers through which ions do not diffuse readily. A fourth line of 

 evidence for this theory comes from Overton's own experiments. He found 

 an almost perfect correlation between the lipoid solubility of hundreds of 

 organic compounds and the permeability of the cytoplasmic membranes to 

 them. On the other hand, sugars, salts, and other lipoid-insoluble substances 

 showed practically no penetration into the cells at all. We now know that 

 the terms lipoid-soluble and lipoid-insoluble correspond very closely to the 

 modern terms of non-polar and polar, respectively. 



While Overton's experiments seemed to show that the cytoplasmic mem- 

 branes are relatively impermeable to polar compounds, later work has not all 

 supported this generalization. It is true that polar compounds often penetrate 

 with much greater difficulty than non-polar compounds and that the perme- 

 ability of a given membrane to them may fluctuate, but the membranes are, 

 at times at least, permeable to them. Moreover on a priori grounds it is 

 evident that the membranes must be permeable to sugars, salts, etc. at least 

 part of the time, since in the majority of cells most of these compounds pre- 

 sent must have entered the cell at some time or another during its life history. 



Some investigators hold that the lipoid solubility theory is essentially a 

 correct representation of the mechanism of cytoplasmic permeability. Polar 

 compounds would not be completely insoluble even in a lipoidal layer, and 



