Glucose transport through cell membranes of modified lipid fluidity

Carrier-mediated transport of glucose in human erythrocytes and 3T3 mouse fibroblasts was examined at different lipid viscosities of the cell membrane. Rigidification of the membrane lipid layer was accomplished by incorporation of cholesterol or one of the hydrophilic esters, cholesteryl hemisuccinate or cholesteryl betainate, whereas fluidization was accomplished by cholesterol depletion. In both cells the dependence of the maximal rate of glucose transport at 37 degrees C, Vmax, on the lipid microviscosity of the cell plasma membrane, eta, is of a similar pattern which does not obey simple diffusion considerations. When the eta value of untreated cells is slightly increased (10-20%), Vmax increases to a peak value, beyond which a further increase in eta progressively reduces it. Decrease of the natural eta is also accompanied by a progressive decrease of Vmax. This general pattern was also observed for the transport of alpha-aminoisobutyric acid in 3T3 fibroblasts (unpublished results). A theoretical analysis of the dependence on eta of the transport turnover number and of the accessibility of carrier sites was carried out in order to account for this behavior. On the basis of this analysis, a general expression for the dependence of Vmax on eta, which fits reasonably well with the experimental data, was derived. This expression is also valid for the dependence on eta of the overt activity of membrane-bound enzymes and receptors.