O permeability of lipid bilayers is low, but increases with membrane cholesterol.

Oxygen on its transport route from lung to tissue mitochondria has to cross several cell membranes. The permeability value of membranes for O (P), although of fundamental importance, is controversial. Previous studies by mostly indirect methods diverge between 0.6 and 125 cm/s. Here, we use a most direct approach by observing transmembrane O fluxes out of 100 nm liposomes at defined transmembrane O gradients in a stopped-flow system. Due to the small size of the liposomes intra- as well as extraliposomal diffusion processes do not affect the overall kinetics of the O release process. We find, for cholesterol-free liposomes, the unexpectedly low P value of 0.03 cm/s at 35 °C. This P would present a serious obstacle to O entering or leaving the erythrocyte. Cholesterol turns out to be a novel major modifier of P, able to increase P by an order of magnitude. With a membrane cholesterol of 45 mol% as it occurs in erythrocytes, P rises to 0.2 cm/s at 35 °C. This P is just sufficient to ensure complete O loading during passage of erythrocytes through the lung's capillary bed under the conditions of rest as well as maximal exercise.