Transmembrane Protein Effects on Lipid Bilayer Oxygen Permeability

Abstract

Oxygen (O2) diffusion across lipid bilayers is required for oxygen delivery to tissues. Diffusive transport is especially important in tissues where vessels are occluded or sparse. Atomistic molecular dynamics simulations have provided valuable insights into the mechanism and kinetics of oxygen transport at the membrane level. The role of lipids has been investigated in numerous studies, but proteins have generally not been included in the models. As a step toward a more authentic cell membrane model, we recently studied the effects of an ungated potassium channel protein on lipid bilayer oxygen permeability and related biophysical properties. That work provided initial support for the hypothesis that transmembrane proteins nonspecifically reduce the oxygen permeability of membranes, by reducing the fraction of permeable surface area and the effective diffusion coefficient for oxygen. Here, atomistic molecular dynamics simulations are used to test the hypothesis further, by considering several alpha-helical transmembrane proteins of varying size and biological function. Effects of the proteins are considered in the context of 1-palmitoyl,2-oleoylphosphatidylcholine (POPC) and POPC/cholesterol (1:1 mole ratio) bilayers. The current results support nonspecific reduction of permeability by transmembrane proteins that depends on both the in-plane area of the protein and the extent (circumference) of the protein-lipid interface. The protein effects are less dramatic in membranes incorporating cholesterol, perhaps due to packing defects at the protein-lipid interface in the relatively ordered POPC/cholesterol bilayers. The apparent solubility (partition coefficient) of oxygen within the membrane is diminished by cholesterol but enhanced by protein. These findings indicate that transmembrane proteins are a key factor in membrane permeability and that studies omitting them should be interpreted with caution.