Role of Lipid Composition in Gas Permeation across Biological Membranes

Abstract

Gas molecules dissolved in an aqueous environment are pre-dominatly in their hydrophilic charged state because of their respective acid/base equilibria. Overton's rule suggests that permeation of small charged molecules across the membrane boundary is highly restricted and must occur either in their neutral form or through a dedicated transport mechanism. There has been experimental evidence to the effect that the water channel family, Aquaporins, may be responsible for the permeation of neutral gas molecules such as CO2, NH3, and O2 across biological membranes. This is in apparent contrast to the observation that the permeation rate of neutral gas molecules across pure lipid bilayers is mostly unhindered. It is hence of interest to test the hypothesis the lipid composition of biological membranes may result in a vastly different in gas permeability as composed to pure model membranes.The lipid composition of physiological membranes is highly complex and further involves asymmetry in the two leaflets. Also, a major component of the cellular lipid bilayers involved in gas permeation, such as those surrounding Red Blood Cells (RBCs), is cholesterol. Cholesterol is known to have a strong clustering effect that increases the packing of the lipids in the membrane. It is possible to study the role of lipid composition and asymmetry through molecular dynamics (MD) simulations by reconstructing atomistically the important characteristics of physiological membranes. Here we present preliminary results of the permeability of model physiological membranes based on atomistic MD simulations.