10 



MACROMOLECULAR COMPLEXES 



tially linear rise. The extent of the lag period is determined mark- 

 edly by the initial insulin concentration, as is the slope of the near- 

 linear portion of the curve. A comparison of the reaction kinetics 

 obser\ed with the growth of seeded fibrils and in the absence of 

 seeding suggests that the fibril is first initiated by a nucleation 

 reaction which involves the cooperative effects of three or four in- 

 teracting units (dimers). Thus the rate of nucleation varies with 

 the 3d or 4th power of the insulin concentration. After initiation, 

 when the fibril has achieved a reasonable size, the fibril grows as 

 a function of its surface area and the 1st power of the free insulin 

 concentration. The cooperative effect established during nucleation 

 is perpetuated, and the surfaces (particularly of the ends) of the 

 fibril present to the entering insulin unit the correct cooperative 

 configuration necessary for bonding. 



One particularlv interesting consequence of this type of mech- 

 anism is that most of the fibrils are initiated during the lag period 

 of the reaction. Those which are initiated during the first few 

 minutes of the lag period dominate the reaction, in the sense that 

 thev are responsible for removing most of the insulin. The fibril 

 population at the end of the reaction appears to be relatively 



16. lA 



485A 



"■^1 



- ~-J 



Fig. 1. Diagram of a fibril nucleus, 

 (From Waugh, 1957.) 



lustroting a cooperative interaction. 



