572 BERNARD D. DAVIS 



Early studies on cell membranes naturally focused on their resemblance 

 to the simple physicochemical models provided by artificial semipermeable 

 membranes, in which penetration took place by diffusion through pores. 

 And, indeed, the kinetics of the penetration of certain substances into cells, 

 including dissolved gases and some very small organic molecules, could be 

 accounted for by this mechanism. Many large molecules, however, 

 exhibited anomalously high values; and studies of certain homologous 

 series showed a parallelism between rate of penetration and lipid solubility 

 (which increased with size). Hence penetration by solution in lipids, in 

 which biological membranes are known to be rich, was recognized as 

 another significant mechanism. Both these mechanisms were compatible 

 with the view of a biological membrane as a relatively homogeneous 

 undifferentiated structure — perhaps a somewhat porous double layer of 

 protein and lipid. 



Nevertheless, the behaviour of most of the metabolically important 

 substances that have to penetrate into cells, including sugars, amino acids, 

 and inorganic electrolytes, did not fit either of these mechanisms ; and a 

 major development in the nineteen-thirties was the recognition (at least 

 among the band of specialists in this field) that with most substances 

 penetration into cells involves specific transport systems. In contrast to 

 the diffusion mechanisms previously described, the rate of transport by 

 these specific systems does not increase indefinitely as a function of 

 permeant concentration but instead exhibits saturability, implying a mass- 

 law interaction between permeant and transport system. This conclusion 

 implies functionally differentiated regions of the membrane. It is this 

 aspect of the cell membrane, rather than its generalized or average 

 properties, that now seems to deserve most attention, much as the study 

 of specific enzymes and intracellular organelles has displaced the study of 

 "protoplasm". 



Two groups of specific transport systems have been recognized. The 

 first, of which the sodium pump is an example, can carry out active trans- 

 port — that is, it can move its permeant to a region of higher thermodynamic 

 potential. The second group, such as those responsible for entry of sugars 

 into erythrocytes, cannot transport uphill : with a non-metabolized sub- 

 stance these systems can only accelerate the approach to equilibrium (i.e. 

 to the same chemical potential on both sides of the membrane), and with a 

 metabolizable substance the rate of utilization is accelerated. 



This second kind of specific transport has been called facilitated 

 dijfusion by Danielli. Though this term is widely used it does not seem 



bacteria are unique in lacking steroids. It is therefore quite possible that future 

 analysis will reveal significant diflferences as well as broad similarities in the 

 structure and in the function of transport systems in bacterial compared with 

 other biological membranes. 



