The effect of fatty acid substitution of membrane phosphatides on a number of surface-mediated phenomena in EL-4 cells was examined. Tumor cells were grown in the presence of fatty acids that could be expected, on the basis of their physical properties, either to stiffen or fluidize the plasma membrane. Substitution of EL-4 cell membrane phosphatides with as much as 74% nonade-canoic acid (19:0) had no effect on either conjugation with effector cells or subsequent cytolysis by the effector cells. Substitution with linolenic acid (18:3) or elaidic acid (18:1trans) likewise affected neither conjugation nor cytolysis. Substitition with these fatty acids also had no effect on the susceptibility of EL-4 cells to cytolysis by antibody plus complement. On the other hand, the rate of patching of H-2 surface antigens was very sensitive to substitution by both 19:0 and 18:3. Although not conclusive, these results suggest that alterations of the fluid state of the membrane that affect lateral movements of surface proteins may not affect cytolytic processes.

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