Microscopic Insights into Biological Relevance of Membrane Channels in Gas Transport across Lipid Membranes

Abstract

Membrane transport of small, non-polar gas molecules, such as O2 and CO2, is among fundamental processes of living cells. Because of their size and chemical properties, these molecules may unimpededly transit through the lipid phase of the membrane. However, varying degrees of gas permeability in membranes with different lipid compositions have been reported experimentally, suggesting involvement of protein channels, particularly aquaporins (AQPs), in gas transport across membranes. To account for membrane heterogeneity and to probe potential roles of AQPs in gas transport, we performed extensive MD simulations of gas diffusion through lipid membranes. The systems simulated included POPC bilayers embedded with an AQP tetramer (i.e., AQP1, AQP5 or AQP7), and protein-free lipid bilayer mixtures of POPC, cholesterol (CHL) and sphingomyelin (SM) or DPPC. Each of them contained an excess amount (125 molecules) of a gas species and was simulated for several hundred nanoseconds. Since the gas molecules were allowed to diffuse freely, their permeability coefficients were directly estimated by measuring their flow through the lipid and protein phases. The results showed that gas molecules diffused through the membrane via monomeric water and hydrophobic central pores of AQPs, and via the lipid phase. For fluid-like membranes (e.g., 100% POPC) which exhibited high gas permeability, AQPs would not facilitate the permeation. Highly-ordered or gel-like membranes (e.g., 100% SM and 50:50 SM:CHL or DPPC:CHL), on the other hand, exhibited reduced gas permeability as low as or even lower than through AQPs, suggesting that in such conditions, AQPs would become imminent in facilitating gas transport. Consistently with experimentally observed low gas permeability in high SM-CHL containing membranes, such as those of erythrocytes and ocular lens, our study suggests biological significance of protein-facilitated gas permeation across membranes.