46 



Cellular Structure and Activity 



material, whether that may prove to be long 

 known or yet to be discovered. 



FIBROUS SYSTEMS OF CYTOPLASM 



The linear, fibrous array is geometrically, 

 physically and chemically well adapted to 

 subserve a number of fundamental biological 

 processes. It permits the specific adlineation 

 and segregation of chemical and biological 

 entities, as in chromosomes. It provides me- 

 chanical strength and rigidity: the tensile 

 strength of collagen fibers may be as high as 

 100 kg./cm.2 (as high as some metals). Con- 

 tractility is almost imiquely a property of 

 fibrous material. Most fibers of biological 

 origin, particularly those composed of pro- 

 teins and their complexes, are capable of 

 contraction when subjected to appropriate 

 chemical environment. To grasp the proc- 

 esses underlying the basic phenomena of 

 growth and differentiation, insofar as they 

 concern the molecular machinery of the cell, 

 the investigator must delve fairly deeply into 

 the physical and chemical mechanisms of 

 contractility. This involves the submicro- 

 scopic fibrous lattices responsible for sol-gel 

 transformation as well as the more obvious 

 fibrous systems described in classical cy- 

 tology. 



Most of our detailed knowledge about 

 fibers has been derived from a study of pro- 

 teins, polysaccharides, nucleic acids and 

 their conjugates which can be purified and 

 subjected to physical chemical analysis. This 

 knowledge has been of great value in studv- 

 ing the intracellular fibrovis systems which 

 have not yet been isolated and characterized. 

 Accordingly, it will be useful to discuss a 

 few of the salient features of purified pro- 

 teins as well as to describe the far less per- 

 fectly understood intracellular systems. 



POLARIZATION OPTICAL ANALYSIS 



Protein fibers usually manifest positive in- 

 trinsic and form birefringence. This permits 

 detection, in living cells, of fibrous arrays and 

 their direction of orientation even though 

 the structures are too thin to be resolved by 

 the light microscope. This is made possible 

 by high sensitivity of the polarization optical 

 method (Swann and Mitchison, '50; Inoue, 

 '51). 



Application of the Wiener theory of form 

 birefringence led to the deduction that fibrils 

 which show positive form birefringence are 

 composed of still finer fibrous structures 

 whose thickness is small with respect to the 



wave length of light. This deduction has 

 been verified with the EM in each case so 

 far investigated. Indeed, electron microscopy 

 has shown that the fibrous elements respon- 

 sible for the form birefringence may occur 

 as filaments of characteristic width, fre- 

 quently about 100 to 300 A. 



When lipid or nucleic acid is associated 

 with fibrous proteins their presence can be 

 deduced from polarized light examination, 

 since the sign of their birefringence is oppo- 

 site to that of fibrous proteins. 



X-RAY DIFFRACTION ANALYSIS 



The eventual aim of x-ray diffraction 

 crystallography is to determine not only the 

 major structural features of the molecule but 

 also the exact position of each atom within 

 the molecule. This has not yet been possible 

 with the crystalline, globvilar proteins which 

 produce hundreds or thousands of diffraction 

 spots in the x-rav pattern. The task is enor- 

 mously more difficult in the case of the 

 fibrous proteins whose patterns may be rela- 

 tively poor in diffractions. 



The polypeptide chain is the structural 

 unit of fibrous proteins. The diffraction 

 analysis centers around the determination 

 of the configuration of the polypeptide 

 chains, the interchain relationships and the 

 larger structviral features which relate to 

 molecular domains or supermolecvxlar pat- 

 terns. 



Configuration of Polypeptide Chains. In cer- 

 tain types of fibrous proteins, such as silk, 

 feather keratin and highly stretched hair 

 and muscle protein, the polypeptide chains 

 are thought to be nearly fully extended (Ast- 

 bury's beta type). Extended chains may form 

 fabrics which Pauling and Corey ('51a) call 

 "pleated sheets" because the two chain bonds 

 of the a carbon atom form a plane which is 

 perpendicular to the plane of the sheet, form- 

 ing "pleats." However, in most fibrous, and 

 probably globular, proteins the chains have 

 a folded configuration (Astbury's alpha type) 

 whose detailed configuration may differ 

 among the various types of proteins. 



The precise configuration of the folded 

 chains has not yet been unequivocally dem- 

 onstrated in any protein. The best evidence 

 at present favors the view that the chains 

 may be helically coiled, the pitch and num- 

 ber of amino acid residues per tvirn varying 

 with different proteins (Pauling and Corey, 

 '51b,c; Bear, '52; Bull, '52). For a discus- 

 sion of recent developments in this field see 

 Kendrew ('54) and Edsall ('54). 



