June 27, 1913] 



SCIENCE 



965 



of sugar, mannite or giycoeoll of the same 

 osmotic pressure (of about 6 atmospheres). 

 But if to an ni/S NaCl solution we add 

 (e. g.) alcohol in sufficient quantity to 

 double the total osmotic pressure of the so- 

 lution, it is found that there is no percept- 

 ible increase in its osmotic action on the 

 muscle; in other words, the alcohol acts as 

 if it entered the cell with the same readi- 

 ness as the water. Many other substances 

 show a similar power of freely entering the 

 cell; others like urea, glycol and glycerine 

 also enter, but more slowly. Similar obser- 

 vations in both animal and plant cells have 

 shown that readiness of entrance into cells 

 is a property that is closely correlated with 

 solubility in fats or fat-like substances, in- 

 cluding lipoids like lecithin. Substances 

 not so soluble usually gain entrance slowly 

 or imperceptibly. Overton drew from these 

 facts the conclusion that the outer limit- 

 ing layer or plasma-membrane of living 

 cells consists in large part of lipoids, and 

 that the characteristic osmotic properties 

 of the cell depend on the presence of these 

 substances in the membrane. Since sub- 

 stances that dissolve in lipoids will pass 

 readily through lipoid-impregnated parti- 

 tions, this view explains why plasma-mem- 

 branes are in fact readily permeable to such 

 substances as a class. In its detailed appli- 

 cation Overton 's view has met with consid- 

 erable opposition; thus, according to Over- 

 ton, intra-vitam dyes like neutral red and 

 methylene blue enter cells readily because 

 of their solubility in lipoids ; a certain num- 

 ber of exceptions to this rule have been 

 pointed out by Ruhland and others ; but in 

 spite of these discrepancies there seems no 

 doubt— when the whole of the evidence 

 is considered — of the truth of Overton's 

 main contention that lipoid-solubility 

 strongly furthers the ready entrance of 

 substances into cells. Traube believes that 

 the degree of surface-activity, rather than 



of simple lipoid-solubility, is the determin- 

 ing factor; this property shows a general 

 parallelism with the lipoid-water partition- 

 coefficient, and hence also with the readi- 

 ness of penetration. But there appear to 

 be more exceptions to Traube 's rule than to 

 Overton's, while there are other and inde- 

 pendent indications that the surface-films 

 of cells are characteristically rich in lip- 

 oids ; for instance, the fact that in the eggs 

 of sea-urchins and other animals lipoid-sol- 

 vents are especially effective in causing the 

 formation of fertilization membranes (a 

 typical surface-effect) and in initiating 

 cell-division; also the facts which I shall 

 cite presently, showing that lipoid-solvents 

 are characteristically effective in altering 

 the permeability of the plasma-membranes 

 and in modifying their resistance to altera- 

 tion by cytolytic substances. 



I dwell upon these researches here be- 

 cause of the light which they throw on the 

 question of the constitution of the plasma- 

 membranes of cells, including those of the 

 irritable tissues. They , indicate that the 

 membranes — and perhaps surface-struc- 

 tures in general — are especially rich in 

 lipoids. Now lipoid-soluble substances will 

 tend, by the operation of the partition- 

 law, to concentrate in the lipoids of the 

 tissue ; they will thus tend to gather in the 

 membranes, and in so doing they will neces- 

 sarily modify the physical state of these 

 structures and so influence their physiolog- 

 ical properties. We have already seen that 

 the most striking effect which lipoid-sol- 

 vents produce on irritable tissues is to 

 modify their irritability, and under certain 

 conditions to suppress it altogether. This 

 suggests that the membranes have a special 

 relation to stimulation. We shoiild expect 

 on a priori grounds that the excitatory 

 apparatus of the cell should be externally 

 situated ; and we are thus led to inquire if 

 there is other and independent evidence 



