O2 permeability of lipid bilayers is low, but increases with membrane cholesterol

Abstract

Oxygen on its transport route from lung to tissue mitochondria has to cross several cell membranes. The permeability value of membranes for O2 (PO2), 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 PO2 value of 0.03 cm/s at 35 °C. This PO2 would present a serious obstacle to O2 entering or leaving the erythrocyte. Cholesterol turns out to be a novel major modifier of PO2, able to increase PO2 by an order of magnitude. With a membrane cholesterol of 45 mol% as it occurs in erythrocytes, PO2 rises to 0.2 cm/s at 35 °C. This PO2 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.

The HVCN1 voltage‐gated proton channel contributes to pH regulation in canine ventricular myocytes

“…2017; Al‐Samir et al . 2021). Thus, one can speculate that the exchange of t‐tubular and extracellular fluids, driven by mechanical forces (McNary et al .…”

“…Furthermore, t-tubule membranes have high levels of cholesterol, which is reported to make membranes relatively impermeable to CO 2 , which should prevent significant leakage of CO 2 back into the cytosol. Interestingly, recent studies show that membrane permeability of O 2 increases as cholesterol increases (Dotson et al 2017;Al-Samir et al 2021). Thus, one can speculate that the exchange of t-tubular and extracellular fluids, driven by mechanical forces (McNary et al 2012) may have the potential to contribute not only to CO 2 disposal but also to O 2 delivery.…”

Red Blood Cell Membrane Cholesterol May Be a Key Regulator of Sickle Cell Disease Microvascular Complications

“…In addition to modulating the activity of specific membrane proteins, the high C/PL ratio of RBC may facilitate gas exchange, as the low oxygen permeability of phospholipid lipid bilayers increases with enrichment of membranes, with cholesterol reaching a plateau between 40 and 50% [2]. Itel et al [3] reported the first experiments showing that the permeability of cell membranes for CO 2 appears to be regulated by membrane cholesterol content and membrane protein gas channels over a wide range spanning 2 to 3 orders of magnitude.…”

The Chemical Reactivity of Membrane Lipids

“…In a similar vein, the permeability of dissolved gases, including oxygen , and carbon dioxide, is decreased by the presence of cholesterol. In some systems, however, the presence of cholesterol has been found to increase oxygen permeability by an order of magnitude …”

“…In some systems, however, the presence of cholesterol has been found to increase oxygen permeability by an order of magnitude. 50 In mixtures containing cholesterol that exhibit phase separation into liquid ordered (L o ) and liquid disordered (L d ) phases, the L o phase has lower water permeability. 29,51 However, the difference in water permeability between L o and L d is significantly lower than the difference between the permeability of gel and fluid phases of single-component lipid membranes.…”