O₂ 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 O₂ (P_O2), 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 O₂ fluxes out of 100 nm liposomes at defined transmembrane O₂ 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 O₂ release process. We find, for cholesterol-free liposomes, the unexpectedly low P_O2 value of 0.03 cm/s at 35 °C. This P_O2 would present a serious obstacle to O₂ entering or leaving the erythrocyte. Cholesterol turns out to be a novel major modifier of P_O2, able to increase P_O2 by an order of magnitude. With a membrane cholesterol of 45 mol% as it occurs in erythrocytes, P_O2 rises to 0.2 cm/s at 35 °C. This P_O2 is just sufficient to ensure complete O₂ loading during passage of erythrocytes through the lung's capillary bed under the conditions of rest as well as maximal exercise.