J. F. DANIELLI 



Thus the accumulated evidence from kinetic studies shows that : 



(a) plasma membranes are homogeneous lipoid membranes, to a first approxima- 

 tion. 



(b) very small molecules penetrate more rapidly than would be expected for a 

 lipoid membrane, and their permeability constants have anomalous temperature 

 coefficients. 



(c) some larger polar molecules penetrate more rapidly than expected, and their 

 permeability constants have anomalous temperature coefficients. 



(d) for larger molecules abnormally rapid penetration is shown by a very limited 

 range of molecular structures. 



(e) only a small proportion of the total plasma membrane area displays perme- 

 ability properties which would not be expected of a homogeneous lipoid layer. 



(4) The nature of the membrane process 



To approach the problem of the mechanism of abnormally rapid penetration, we 

 must first state the mechanism of normal permeation of a lipoid layer. This may be 

 considered to involve three steps. 



(a) Entry into the membrane: this involves breaking the hydrogen bonds linking a 

 molecule to water, the overcoming of van der Waals' forces, and the formation of a 

 hole in the membrane large enough to accommodate the penetrating molecule. 



(b) Diffusion through the membrane: this involves mainly the overcoming of van der 

 Waals' forces between hydrocarbon chains and between hydrocarbon chains and the 

 diffusing molecules. 



(c) Exit from the membrane: this involves processes the reverse of (a). 



Any one of these three steps will prove limiting for an appropriate molecular 

 species; e.g. for highly polar molecules such as erythritol, (a) is limiting because of 

 the number of hydrogen bonds which must be broken before the molecule can break 

 away into the membrane. For acetamide, steps (a) and (c) are relatively unimportant, 

 so that the viscous resistance encountered in diffusing through the membrane be- 

 comes the limiting factor. With octyl alcohol the number of hydrogen bonds involved 

 is relatively small, but on leaving the membrane a large hole must be formed in the 

 water to accommodate the eight CH 2 groups: this requires a good deal of energy and 

 hence step (c) is limiting. 



In view of these facts, how can we account for abnormally rapid permeation? 



For very small molecules an explanation could be, and perhaps often is, found in 

 the existence of more than one phase in the lipoid layer (Danielli, 1949). We can 

 envisage that very small molecules may be able to penetrate through all the various 

 lipoid phases, whereas larger molecules would be able to pass through only the less 

 densely packed molecules. This, however, does not explain how a very polar molecule 

 such as glucose may penetrate abnormally fast. 



Abnormally rapid penetration of a polar molecule such as glucose can occur only if 

 a special mechanism is provided for breaking its hydrogen bonds with water, e.g. if 

 the membrane contains a carrier molecule which will form hydrogen bonds with the 

 polar molecule, so that the complex between the two forms no hydrogen bonds with 

 water. This would not offer any very satisfactory explanation of why very small 



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