Modulation of membrane organization in normal and transformed cells: the effect of cytochalasin B

The organization of the plasma membrane of contact inhibited cells (3T3) and transformed cells (SV3T3) differs significantly. Studies employing freeze fracture electron microscopy demonstrated that the plasma membranes of 3T3 cells contain aggregated intramembranous particles (PMP), whereas PMP are randomly distributed in SV3T3 cells when prepared in either medium alone, in sucrose or in glycerol. There were also significant changes in the distribution of PMP in 3T3 cells following cell contact and during the cell cycle. Further studies showed that vinblastine, colchicine and lumicolchicine induce a dose and time dependent aggregation of PMP in SV3T3 cells without significantly affecting the membrane ultrastructure of 3T3 cells. Electron spin resonance studies also showed differences in the order of membrane lipids in 3T3 and SV3T3 cells in the native state and following exposure to membrane active drugs. The current studies extend these observations and demonstrate that cytochalasin B (CB) induces a reversible dose and time dependent disaggregation of PMP in 3T3 cells but shows minimal effects on the membranes of SV3T3 cells. Thus 10^-7 to 10^-9 M vinblastine promotes PMP aggregation and 0.01 to 0.5 μg/ml CB promotes PMP disaggregation. This suggest that changes in the interaction of plasma membrane particles (PMP) with colchicine and cytochalasin B sensitive, membrane associated proteins can modulate the organization of the plasma membrane. These changes in membrane structure may influence the activity of membrane enzymes, such as adenylate cyclase or transport systems, that may be critical to the control of cell proliferation.