126 KERATIN AND KERATINIZATION 



in vitro. To do this it would be necessary to isolate a precursor in a fonn 

 still capable of forming fibrils, either from the germinal tissues of the 

 epidermis or from the fibres themselves, by reversing the process of 

 fibrogenesis. Unfortunately, largely as a result of the chemical reactions 

 involved in keratinization (Chapter 6), it has proved impossible to redis- 

 solve keratin without gross modifications of its structure. Further, it has 

 also proved impossible to separate the unaltered precursor from the 

 germinal cells. 



For these reasons our views on fibrogenesis in keratin must be based on 

 reasonable inferences drawn from a study of more tractable systems and 

 checked against a background of direct observation of cellular events. 



Logically we may distinguish two methods of fibrogenesis : either (a) a 

 macromolecular precursor is formed first and subsequently aggregated to 

 form a fibril ; or (b) micro-units, e.g. amino acids are directly built into the 

 growing fibril and no macromolecular precursor is involved. In many 

 fibrous systems we know experimentally that (a) is the actual course 

 followed and it may well always be the case. No macromolecular pre- 

 cursor can be demonstrated for the fibrous hard keratins; but while 

 admitting that we do not know precisely how polypeptides are formed, 

 we know that it involves the participation of other large molecules, such as 

 RNA particles, and it is difficult on spatial grounds to see how these large 

 bodies — larger in diameter than the filaments themselves — can be brought 

 into position at the growing points of the filaments. Furthermore, no 

 close association of particles and fibrils is in fact observed in the cells of the 

 hair follicle (Plate 11). Thus it may be concluded that a soluble precursor 

 exists transiently. The considerable quantities of amorphous protein 

 demonstrable electron-microscopically after special staining may, in part, 

 represent this precursor. 



In a general sense, we can anticipate that the nature of the aggregation 

 is likely to be much influenced by the shape of the precursor molecule, 

 " interaction profile " (Hodge, 1960), or by modifications in its shape 

 which accompany fibrogenesis. In some systems a more-or-less iso- 

 diametric molecule may simply aggregate without marked internal change, 

 and the process is then very similar to crystallization (see also Rees, 1951). 

 In others, preliminary modifications of structure precede aggregation as is 

 the case with the fibrinogen-fibrin system (Lorand, 1952; Lorand and 

 Middlebrook, 1952). Other unexpected, even bizarre events should not be 

 ruled out. For example, Rudall (1955-6), in attempting to trace out the 

 development of the fibrous ribbons of the egg case of a mantid, discovered 

 that lumps of precursor are first formed into vacuolated droplets which are 

 thinned, flattened and drawn out to yield the fibrous ribbons. It is 

 obviously necessary to treat each case as a special case, if this is at all 

 possible. We can only review very briefly a few examples of systems which 



