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Water permeability of Friend leukemia cells was studied by 170 nuclear magnetic resonance during differentiation induced by dimethyl sulfoxide (Me2SO). While in noninduced cells water permeability was essentially constant during the growth period, in the Me2SO-induced cells there were two distinct periods at which the water permeability was increased by at least an order of magnitude. These periods correspond to approximately one doubling time and 6 days of growth. This change in water permeability is not due to direct interaction of Me2SO with the membrane but must be ascribed to structural changes in the membrane during the course of differentiation.Friend leukemia cells (FLC) provide an excellent model system for the study of cell differentiation (1-3). These cells proliferate in culture as immature blast cells and can be induced to differentiate by several chemical agents, of which dimethyl sulfoxide (Me2SO) has been the most extensive used (3-6). Treatment of these cells with 2% (vol/vol) Me2SO permits the cells to begin mouse hemoglobin synthesis. The maturation sequence of these chemically stimulated cells is accompanied by heme and globin production and appears to parallel normal erythropoiesis with the accumulation of erythrocyte-specific proteins (hemoglobin, spectrin, and glycophorin) (3, 7). A decrease in cell volume corresponding to an increase in membrane microviscosity and the amount of cells producing hemoglobin was observed (8)(9)(10). Indications of significant modifications provoked in the cell membrane during Me2SO-induced differentiation are expressed in a decrease in the permeability and fluidity of the cell membrane (8, 10) and in changes in the sensitivity to agglutination by lectins (7). The mechanism by which Me2SO stimulates differentiation and the primary site of action are unknown.Differential scanning calorimetry measurements indicated that Me2SO and other inducing agents cause a decrease in phospholipid membrane fluidity, suggesting that the induction of differentiation by these agents might be the result of their interaction with the cell membrane (11). Because it is thought (12) that the fluidity of phospholipid membranes is related to their water permeability, we decided to conduct an independent study of the water permeability of FLC membranes during their various stages of differentiation. Our method uses NMR relaxation measurements of 170 from cell preparations in 170-enriched water.NMR has recently been used to study water permeability of membranes in two systems, viz. erythrocytes and phospholipid vesicles (13-18). The principle of the method is based on the ability to distinguish separate water nuclei signals ('H or 170) from the inner (cell or vesicle) compartment and the bulk water. The results of the water permeability studies show that, during the course of Me2SO-induced differentiation, the water permeability in FLC is not constant, nor does it vary montonically with time. Instead we found two short periods (after one doubling time and 4 days later) at whic...