Time-dependent cell membrane fluidity changes induced by tumor necrosis factor-alpha and transmission electron microscopy morphologic investigation

The time-dependent tumor necrosis factor-alpha (TNF)-induced changes in the plasma membrane lipid bilayer have been investigated in K562 cells, a human chronic myelocytic leukemia cell line, using spin label electron spin resonance techniques. Treatment of K562 cells in suspension culture with TNF for as long a time as 6 h caused an increase in cell membrane fluidity (CMF) and returned to the level of control cells at 12 h. But, conversely, by 24 h after beginning of treatment, the rigidity of CMF was increased and remained so for at least 2 days. The change of TNF-induced CMF in K562 cells was biphasic, but not in Daudi cells, a human malignant lymphoma cell line. Thus, the TNF-induced perturbation of membrane structure is specific. The late increase in membrane rigidity may have a different underlying mechanism from that of the early change. While the early and transient change probably is related to signal generation and transmission, the later and persistent change may be an aspect of the phenotype of TNF-treated cells and may reflect changes in the plasma membrane-cytoplasmic complex. In addition, membrane changes induced by TNF have an ultrastructural correlate.