52 



Cellular Structure and Activity 



portantly on ionic strength and on linkage 

 through particular types of groups, such as 

 SH groups. 



A good example of this type is the muscle 

 protein, actin. In solutions of low ionic 

 strength the viscosity is relatively low and 

 the actin exists as globular particles. In- 

 crease in ionic strength increases the viscosity 

 markedly due to the formation of fibers by 

 the adlineation or polymerization of globular 

 actin molecules. Redviction of ionic strength, 

 as by dialysis, reconverts the fibers to globu- 

 lar molecules. This type of reversible process 

 may play an important role in muscle con- 

 traction. According to Straub and Feuer 

 ('50) the globular actin contains ATP as a 

 functional group; removal of the terminal 

 phosphate causes the linking of actin mole- 

 cules, in which process SH and Ca may be 

 involved. However, the process requires no 

 enzyme such as ATP-ase. 



Tropomyosin, investigated extensively by 

 Bailey ('48a,b), and thought to be the pre- 

 cursor of myosin, is also capable of reversible 

 globule-fiber transformation depending upon 

 the ionic strength. 



Insulin, whose chemical composition and 

 structure have been thoroughly investigated, 

 normally exists in the form of globular mole- 

 cules but can be converted to the fibrous form 

 by heating in acid solution. The fibrous form, 

 which has no biological activity, can be re- 

 converted to the globular form with full 

 restoration of activity (Waugh, '48). If a 

 minute amount of the fibrous form is added 

 to a solution containing globular insulin, all 

 the insulin comes down in fibrous form. The 

 transformation is quantitative and occurs 

 even in the presence of other proteins and 

 foreign substances (the process has been 

 used by Waugh for in vitro assay of insulin 

 from crude preparations). This suggests the 

 possibility that fibrous proteins may be 

 formed autocatalyticallv in cells once the 

 fibrous form is produced. Whether a similar 

 tvpe of process plays a role in the differentia- 

 tion of cellular proteins remains to be de- 

 termined. 



Enzymatically Induced Fibrilization. The 

 classic example of this type is the conversion 

 of elongate fibrinogen molecules into fibrin 

 under the influences of thrombin. Neglecting 

 the complex system of activators and inac- 

 tivators which control the formation of 

 thrombin from prothrombin, the fibrogenesis 

 may be thus described : Fibrinogen molecules, 

 having dimensions of about 35 X 600 A, un- 

 der the influence of thrombin, are converted 

 into fibrils which appear cross-striated in the 



EM. The axial period is about 230 A (Hawn 

 and Porter, '47). Hall ('49) has demonstrated 

 intraperiod fine structure and suggests that 

 the striations are due to lateral alignment 

 by colloidal forces of components within the 

 fibrinogen molecules. Ferry ('52) has offered 

 additional suggestions concerning the forces 

 and groups involved in the lateral and lon- 

 gitudinal aggregation of fibrinogen mole- 

 cules to form fibrin. It is possible that fibro- 

 genesis of other proteins may involve a 

 complex system analogous to that of blood 

 clotting. 



Underlying the complex, balanced sys- 

 tem of activators and inactivators in blood 

 clotting is the requirement that the clotting 

 system be under the strictest biological con- 

 trol; breakdown of this control may lead to 

 death. 



The mitotic mechanism, with its elaborate 

 spindle and astral fibrilization, may have 

 similar general properties. Many investiga- 

 tors have suggested a basic similarity between 

 the mitotic mechanism and blood clotting 

 and have suggested that it may be no less 

 complex. Heilbrunn ('52) and his associates 

 have emphasized this view and find that cer- 

 tain anticoagulants (heparin, Dicumarol) 

 prevent formation of the mitotic figure in 

 the marine egg. They believe release of 

 Ca** from the cell cortex is an essential 

 factor in cytoplasmic clotting. However, un- 

 til the structural proteins and other compo- 

 nents are isolated and their mechanism of 

 action elucidated, such analogies must be 

 considered speculative. Chargaff ('45, '49) 

 finds that particles from the large-granule 

 fraction of lung cells have high thrombo- 

 plastic action. He suggests that such granules 

 may be involved also in intracellular struc- 

 ture formation. 



Careful polarization optical studies of di- 

 viding cells have been made by Swann and 

 Mitchison ('50), Inoue and Dan ('51) and 

 Swann ('51a,b). The results, well summa- 

 rized by Hughes ('52), indicate that the 

 spindle and asters contain oriented fibrous 

 protein particles which must be very thin 

 (possibly tens or hundreds of Angstrom units) 

 and about as highly hydrated as the proto- 

 plasm surrounding them. Swann concluded 

 that the chromosomes liberate a "structural 

 agent" which affects the organization of the 

 spindle and astral fibers, decreasing their 

 birefringence. No evidence is yet available 

 as to the nature of such a substance. The 

 experiments demonstrate the great sensitivity 

 of the polarization optical method to detect 

 alterations of protoplasmic ultrastructure. 



