Ultrastructural analysis of 3T3 fibroblasts by freeze-cleavage has demonstrated significant changes in cell-membrane structure associated with cell-to-cell contact and malignant transformation. These changes consist of a rearrangement and redistribution of intramembranous particles on the membrane fracture faces exposed by freeze-cleavage. The results show that noncontacted 3T3 cells in low density contain randomly distributed intramembranous particles. With the development of cell-to-cell contacts during the logarithmic phase of growth however, a pronounced aggregation of intramembranous particles is seen. A direct correlation between the degree of cell contact and the percentage of cells showing intramembranous-particle aggregation has been established. By contrast, transformed SV3T3 and SP3T3 cells show no evidence of intramembranous-particle aggregation even at cell densities where cell-to-cell contact is extensive. In view of recent reports that intramembranous particles represent foci of interaction between certain intrinsic membrane proteins and lipids, we propose that cell-to-cell contact of nontransformed 3T3 cells may initiate a change in the distribution of intrinsic membrane proteins associated with intramembranous particles and that these changes may influence control of cell proliferation.
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