62 



Cellular Structure and Activity 



represent a true union between the cells. In 

 such highly localized regions, it would be 

 impossible to tell which part of the surface 

 belongs to which cells.* 



A possibly analogous situation may exist 

 when cells behave "as though they knew 

 their own kind." An example is the recom- 

 bination or self-sorting of coelenterates, hy- 

 droids and sponges with cells of their own 

 kind to the exclusion of heterologous com- 

 binations (Br0ndsted, '36). Immunologically 

 specific cell aggregation or agglutination in- 

 volves both steric matching and the resultant 

 formation of stable bonds between surface 

 molecules. Phenomena of this kind may be 

 partially analyzed by studying the adhesion 

 of cells containing an antibody upon a slide 

 coated with a film of antigen suitably pre- 

 pared. The possibility of intercellular ad- 

 hesion by antigen-antibody like surface bonds 

 was long ago pointed out by Weiss ('41), 

 who has developed the idea in a series of 

 papers (see particularly Weiss, '47, '50). 



In actual biological situations, materials 

 in the intercellular medium play a signifi- 

 cant, sometimes dominating role. The pres- 

 ence of Ca"^* and other multivalent cations 

 is particularly significant (see the reviews of 

 Robertson, '41, and Reid, '43). Such ions may 

 cause cell aggregation in the same manner 

 in which they cause precipitation or co- 

 acervation of colloids. They may actually 

 bond surface molecules of adjacent cells by 

 combination with negative charges in the 

 apposing svirfaces (as they do in built-up 

 layers of fatty acids). Organic cations, such 

 as histones and protamines, may form very 

 stable bonds between negatively charged cell 

 surfaces, such as those of mammalian erythro- 

 cytes (Schmitt, '41). Rouleaux of red cells, 

 presumably involving bonding by certain 

 poorly identified hydrophilic svibstances, rep- 

 resent a similar example. In both cases the 

 bonding is so firm that considerable mechan- 

 ical force is required to separate the cohering 

 cells. 



Valuable analyses of the factors promoting 

 cohesion of epithelial cells are those of Her- 

 mann and Hickman ('48), in which it was 

 possible to estimate the force necessary to 

 separate the epithelium from the under- 

 lying stroma and to separate individual epi- 



* This possibility might be susceptible of experi- 

 mental test if a type of free cell were found capable 

 of being coated with a dispersed fibrous protein such 

 as collagen. By appropriate manipulation of the 

 ionic environment, it might then be possible to 

 cause the cells to aggregate owing to the affinity of 

 the coating collagen filaments for each other. 



thelial cells from each other. Cohesion is 

 decreased by proteolytic enzymes, anionic 

 detergents and high pH (> 9). It was impos- 

 sible to arrive at a common primary cohesive 

 mechanism for cells generally; there is great 

 variability in tissues of different types. 



Connective tissue, the chief components 

 of which have low if any antigenicity, may 

 serve to separate cell types in embryological 

 development, thus permitting strongly in- 

 teracting cells to form tissue anlagen without 

 interference from contact attractions from 

 other adjacent cell types (Weiss, '41). 



Surface interactions between cells may 

 have an important influence on cell shape. 

 Since the tension at the surface of cells is 

 very low (near zero), surface interaction 

 with other cells or with substrate may pro- 

 foundly alter cell shape (assuming that cell 

 volume does not change appreciably during 

 the process). Strong intercellular bonding, 

 causing cells to share sm^faces to a maximal 

 extent, may be expected to lead to the for- 

 mation of tall, columnar epithelia while 

 low interaction leads to flat, cuboidal epi- 

 thelia (Schmitt, '41). Where cells are free 

 to migrate, as in tissue cultures, the con- 

 figuration of the substrate molecules or mac- 

 romolecules may determine the shape of the 

 cells (Weiss, '49; Weiss and Garber, '52). 

 When the cell-to-substrate interaction is low 

 the shape and movements of the cell are 

 determined primarily by properties inherent 

 in the protoplasm, especially in the cortex, 

 favoring ameboid movement (Holtfreter, '46, 

 '47). High cell-to-substrate interaction would 

 cause the cells to flatten and round up when 

 the substrate has an isodiametric molecular 

 organization. When the substrate has an an- 

 isodiametric molecular organization the cells 

 may form elongate processes because of 

 strong interaction with elongate substrate 

 particles having preferred orientation. Such 

 processes lead also to directional migration 

 of cells, depending upon the orientation of 

 substrate particles. Apparent attractions be- 

 tween cells over large distances may be ex- 

 plained by such cell-to-oriented-substrate in- 

 teractions (Weiss, '52). Some evidence 

 indicates that cells may liberate organic 

 materials which influence not only their 

 own contact relations but also directions of 

 migration along macromolecular pathways 

 having preferred orientations (Weiss, '45). 

 Possibly optical and electron optical investi- 

 gation of these phenomena would throw light 

 on the mechanism of such effects. 



In the preceding section, it was suggested 

 that the surface envelope, or plasma mem- 



