Cell Constitution 



61 



muscle strvictvire itself but also on the gen- 

 eral conditions which determine the forma- 

 tion of complex structural patterns in cells, 

 tissues and organisms generally. Thus far 

 only structureless or periodic fibers have been 

 reconstituted in vitro. To reconstitute fibers 

 with aperiodic axial structure, such as chrom- 

 osomes, would seem mvich more difficult be- 

 cause matching points along the chains do 

 not occur periodically but are presumably 

 unique for each point. Nevertheless, con- 

 ditions may be found which would permit 

 even so improbable a process to occur. 



It is not our intention to attempt to force 

 all biological pattern formation into rela- 

 tively simple concepts such as those dis- 

 cussed above. The value of such suggestions 

 has an inverse relation to the complexity of 

 the system. One might, for example, suggest 

 that cells themselves may be able to "crys- 

 tallize" into structural patterns or tissues 

 when the chemical environment is appropri- 

 ate. The experiment, using certain types of 

 free cells, or cells liberated from tissues or 

 embryonic masses by the use of trypsin, 

 seems quite feasible and may be a rewarding 

 exercise, particularly in the analysis of fac- 

 tors concerned in cell-to-cell interaction. It 

 is conceivable that an important new con- 

 cept may emerge from such experiments. 

 However, they should in no way distract 

 attention from the straightforward analyti- 

 cal approach to the complex problems of 

 morphogenetic fields and the genesis of 

 patterns of organization. 



FACTORS INVOLVED IN CELL-TO-CELL 

 AND CELL-TO-SUBSTRATE INTERAC- 

 TION 



For purposes of simplification let us con- 

 sider a somewhat idealized free cell, neglect- 

 ing any siu-face coats or other organic matrix 

 surrounding the cell. The surface will bear 

 electric charges depending upon the dis- 

 sociation of groups in the molecules com- 

 posing the surface envelope. Depending on 

 the ultrastructure and composition of the sur- 

 face molecules the charges will have configu- 

 rational arrays and will be both positive and 

 negative. As indicated in the previous sec- 

 tion, the negative charges will, in general, 

 exceed the positive charges considerably so 

 that the net charge will be negative. 



Surrounding the cell there will be an ion 

 atmosphere consisting of ions of sign op- 

 posite to those of the fixed charges on the 

 surface molecules. These counter ions will be 

 predominantly positive and their density 



will grade out from the surface, forming a 

 diffuse double layer, as exists around charged 

 colloidal particles. The density and extent 

 of the ion atmosphere will depend upon the 

 density of fixed charges on the membrane and 

 upon the ionic strength of the medium sur- 

 rounding the cell. The ionic strength of the 

 medium in vertebrate cells being rather high 

 (between 0.1 and 0.2), the ion atmosphere 

 will not extend far out into the medium. The 

 ion atmosphere exists in an aqueous medium 

 or water shell which forms a part of the 

 fixed environment of the cell. 



At least so far as our idealized cell is con- 

 cerned, cell-to-cell interaction will be gov- 

 erned by the same laws which govern the 

 interaction of colloidal particles. Like cells 

 will have a similar ion atmosphere. Neglect- 

 ing long-range forces (which may actually 

 exist between such giant macromolecular 

 systems), there will be little interaction be- 

 tween cells until they approach within dis- 

 tances equal to their ion atmosphere. There 

 would then be a repulsion (because they bear 

 the same net charge) unless the distribution 

 of positive and negative charges is such as 

 to permit a "matching," in which case the 

 cells would form stable aggregates. It should 

 be pointed out that, particularly in processes 

 of growth and development, the probability 

 that an appreciable fraction of the cells 

 would have the "ideal" properties assumed 

 above is very small. 



Adhesion of cells to other cells and to sub- 

 strates probably depends most importantly 

 upon the formation of electrostatic bonds be- 

 tween groups of opposite sign and also to 

 hydrogen bonds; there is little clear evidence 

 for covalent bonds. 



The force necessary to separate a cell from 

 another cell or from a substrate (hence the 

 stability of the cohesion) depends upon the 

 number and types of linkages between the 

 surfaces. Cells, such as mammalian erythro- 

 cytes, may adhere strongly to a hydrophilic 

 surface such as glass covered with thorium- 

 conditioned stearate layers. This is a non- 

 specific adhesion due to the presence of a 

 large number of attractive groups per unit 

 area in the substrate. When there is steric 

 conformity between the molecular config- 

 urations in the opposing surfaces the prob- 

 ability of strong adhesion is greatly increased. 

 Thus, if the surfaces of two cells contain a 

 fabric of the same fibrous protein (presum- 

 ably not combined at the surface with other 

 substances, thus saturating outwardly di- 

 rected bonds), these proteins might combine 

 to form patches in the interface which would 



