The present position in the field of facilitated diffusion and selective active transport 



A PRELIMINARY ANALYSIS OF THE MEMBRANE PROCESS 



(i) Membrane morphology 



A variety of evidence indicates that the plasma membrane is basically a lipoid 

 layer about 50 A thick, with protein layers adsorbed on either side, i.e. a sandwich 

 structure (Harvey and Danielli, 1934, 1938; Danielli and Davson, 1934; Danielli, 

 1942). In a number of instances this conclusion has been checked by electron- 

 microscopy (Sjostrand and Rhodin, 1953): from the electron-microscopy studies it 

 appears that the total membrane thickness is about 200 A of which about 50 A are 

 lipoid sandwiched between two protein layers each about 70 A thick. In 1933, when 

 this sandwich structure was first proposed, it was suggested that the protein compo- 

 nents consisted of at least one monolayer of adsorbed unfolded proteins, with a second- 

 ary adsorbed layer of globulin. There appeared to be no way in which protein could 

 be incorporated in the lipoid layer, to make a mixed membrane of mosaic structure 

 (Danielli, 1936). Recent developments in the examination of protein structure make 

 it possible to modify this view. 



In the case of haemoglobin, and the same is probably true of many other globular 

 proteins, the structure consists of lamellae. Each lamella has one hydrophobic and 

 one hydrophilic surface, and the lamellae are paired so that in aqueous solution the 

 hydrophobic surfaces are back to back and the protein-aqueous interface is thus 

 mainly hydrophilic. These pairs of lamellae may further associate, specifically, in 

 sets of two or more pairs (Fig. lA). Such associations are fairly stable, but may be 

 broken by hydrogen-bonding substances such as urea. 



In general, if an aqueous pore were opened in a lipoid membrane, surface-tension 

 forces would tend to enlarge the pore, and in the absence of a restraining force would 

 destroy the membrane. If, however, the pore is a slit between two protein lamellae, 

 as indicated in Fig. iB, the same attractions which, in aqueous solution, serve to hold 

 together the hydrophilic surfaces of two haemoglobin lamellae, in the membrane 

 may withstand the low surface-tension forces tending to enlarge the pore. 



Thus from consideration of what is known of plasma membrane morphology, and 

 from the known properties of lipoid molecules, we can envisage a structure which, 

 whilst lipoid to a first approximation, as is known to be the case for many cell mem- 

 branes, has a limited number of polar pores. 



(2) The rate of permeation at constant temperature 



Table III shows experimentally determined permeability constants for various 

 non-electrolytes entering into human erythrocytes and the cells oiChara ceratophylla, 

 compared with the calculated permeability constants for a membrane composed of 

 50 A of hydrocarbon with a viscosity of io 5 times that of water. Within permissible 

 error, the values for Chara are in agreement with the calculated values, and so are the 

 values for human red cells, with three exceptions — those for urea, glycerol and glu- 

 cose — which are very much larger than the calculated values. Thus from considera- 

 tion of rates of permeation it may be shown that the membranes of many cells are, 

 to a first approximation, homogeneous lipoid layers. But there are a few substances 

 which do not fit into this hypothesis. It can be shown, both by calculation and by 



B 7 



