68 



NATURE 



[September i6, 191 5 



chemical combination or in abolition of the essential 

 nature of the process as an adsorption. It would 

 appear that those properties of the surface, such as 

 electric charge and so on, which control the degree of 

 adsorption, are dependent on the chemical nature of 

 the surface. This dependence need not cause us any 

 surprise, since the physical properties of a substance, 

 inclusive of surface tension, are so closely related to 

 its chemical composition. 



There is one practical conclusion to be derived from 

 the facts already known with regard to enzymes. 

 This is, that any simple application of the law of mass 

 action cannot lead to a correct mathematical expression 

 for the rate of reaction, although attempts of this kind 

 have been made, as by Van Slyke. The rate must be 

 proportional to the amount of substrate adsorbed, and 

 this, again, is a function both of the concentration of 

 the substrate and of that of the products. It is, then, 

 a continuously varying quantity. Expressed mathe- 

 matically, the differential equation for the velocity 

 must be something of this kind : — 



f =KC» 



where n itself is an unknown function of C, the con- 

 centration of the substrate or products. 



The hypothesis of control by adsorption gives a 

 simple explanation of the exponential ratio between 

 the concentration of the enzyme and its activity, which 

 is found to be different numerically according to the 

 stage of the reaction. At the beginning, it may be 

 nearly unity; in the middle it is more nearly 0-5, as 

 in the so-called ' square root law ' of Schiitz and 

 Borissov, which is, however, merely an approximation. 

 Simple explanations are also given of the fact that 

 increasing the concentration of the substrate above a 

 certain value no longer causes an increased rate of 

 reaction. This is clearly because the active surface 

 is saturated. Again, the effect of antiseptics and other 

 substances which, by their great surface activity, 

 obtain possession of the enzyme surfaces, and thereby 

 exclude to a greater or less degree the adsorption of 

 the substrate, receives a reasonable account. In many 

 cases, the depressant or favouring action of electrolytes, 

 including acid and alkali, is probably due to aggrega- 

 tion or dispersion of the colloidal particles of the 

 enzyme, with decrease or increase of their total 

 surface. It is to be noted that such explanations are 

 independent of any possible formation of an inter- 

 mediate compound between enzyme and substrate, ajter 

 adsorption has taken place. 



There is a further way in which adsorption plays a 

 part in the chemical processes of cells, including those 

 under the influence of catalysts. It is a familiar fact 

 that the concentration of water plays a large part in 

 the position of equilibrium attained in reversible re- 

 actions of hydrolysis and synthesis. A synthetic 

 process is brought about by diminution of the effective 

 concentration oi water. There are, doubtless, means 

 of doing this in the elaborate mechanisms of cell life, 

 and, in all probability, it is by adsorption on surfaces, 

 which are able to change their "aflfinity" for water. 



I pass on to consider briefly some other cases in 

 which the phenomena at phase boundaries require 

 attention. 



Let us turn our gaze from the interior of the cell 

 to the outer surface, at which it is in contact with 

 the surrounding medium. From the nature of adsorp- 

 tion there can be no doubt that, if the cell or the 

 surrounding liquid contains substances which decrease 

 surface energy of any form, these constituents will 

 be concentrated at the interface. There are many 

 such substances to be found in cells, some of lipoid 

 nature, some proteins, and so on. Further, the ex- 



NO. 2394, VOL. 96] 



periments of Ramsden have shown that a large num- 

 ber of substances are deposited in surface films in a 

 more or less rigid or solidified form. We are thus 

 led to inquire whether these phenomena do not account 

 for the existence of the cell membrane, about which 

 so much discussion has taken place. We find experi- 

 mentally that there are facts which show that this 

 membrane, under ordinary resting conditions, is im- 

 permeable to most crystalloids, including inorganic 

 salts, acids, and bases. There is no other explanation 

 of the fact that the salts present in cells are not only 

 in different concentration inside from that outside, but 

 that there may be absence of certain salts from one 

 which are present in the other, as, for example, 

 sodium in the plasma of the rabbit not in the 

 corpuscles. Moreover, the experiments of Hoeber 

 have shown that electrolytes are free in the cells, so 

 that they are not prevented from diffusion by being 

 fixed in any way. The mere assumption of a mem- 

 brane impermeable to colloids only will not account 

 for the facts, since, as I have shown in another place, 

 this would only explain differences of concentration, 

 but not of composition. The surface concentration of 

 cell constituents readily accounts for the changes of 

 permeability occurring in functional activity, since it 

 depends on the nature of the cell protoplasm, and 

 chemical changes of many and various kinds occur 

 in this system. If such be the nature of the cell mem- 

 brane, it is evident that we are not justified in expect- 

 ing to find it composed of lipoid or of protein alone. 

 It must have a very complex composition, varying 

 with the physiological state of the cell. Indeed, com- 

 plex artificial membranes have been prepared having 

 properties very similar to that of the cell. 



This view that the membrane is formed by surface 

 condensation of constituents of the cell readily 

 accounts for the changes of permeability occurring in 

 functional activity, since its composition depends on 

 that of the cell protoplasm, and chemical changes of 

 various kinds take place in this system, as it is 

 scarcely necessary to remind you. In fact, the cell 

 membrane is not to be regarded as an independent 

 entity, but as a working partner, as it were, in the 

 business of the life of the cell. In the state of excita- 

 tion, for example, there is satisfactory evidence that 

 the cell membrane loses its character of semi-perme- 

 ability to electrolytes, etc. This statement has been 

 shown to apply to muscle, nerve, gland cells, and the 

 excitable tissues of plants, as well as to unicellular 

 organisms. We shall see presently how this fact gives 

 a simple explanation ot the electrical changes asso- 

 ciated with the state of activity. 



If, then, the cell membrane is a part of the cell 

 system as a whole, it is not surprising to find that 

 substances can affect profoundly, although reversibly, 

 the activities of the cell, even when thev are unable 

 to pass beyond the outer surface. The state of 

 dynamic equilibrium between the cell membrane and 

 the rest of the cell system is naturally affected by such 

 means, since the changes in the one component involve 

 compensating ones in the other. Interesting examples 

 of such actions are numerous. I may mention the 

 effect of calcium ions on the heart muscle, the effect 

 of sodium hydroxide on oxidation in the eggs of the 

 sea-urchin, and that of acids on the contraction of the 

 jelly-fish. Somewhat puzzling are those cases in 

 which drugs, such as pilocarpine and muscarine, act 

 only during their passage through the membrane and 

 lose their effect when their concentration has become 

 equal inside and outside the cell. 



The work of Dale on anaphylaxis leads him to the 

 conclusion that the phenomena shown by sensitised 

 plain muscle can most reasonably be explained by 

 colloidal interaction on the surface of the fibres. The 



