Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

49-POS Board 13 INTERPLAY OF CHOLESTEROL AND HEADGROUP EFFECTS ON MEMBRANE OXYGEN PERMEABILITY Qi Wang 1 ; Sally Pias 1 ; 1 New Mexico Institute of Mining and Technology, Chemistry, Socorro, NM, USA Diffusive transport of oxygen (O 2 ) at the level of cell membranes is essential for energy metabolism. Prior studies by our group and others have indicated that cholesterol and increased saturated tail chain length can reduce the permeability of phosphocholine (PC) bilayers by 10- 25% or more. Here, we investigate the interplay of lipid headgroup variations and cholesterol content. Breast tumor lipidomics data indicating that a particular lipid incorporating PE(18:0/18:1) is abnormally high in the cell membranes of aggressive breast tumors. Our hypothesis is that lipid changes promoting increased membrane order, including the smaller phosphatidylethanolamine (PE) headgroup, the longer 18:0 tail, and increased cholesterol content will reduce oxygen permeability and may tend to promote tumor cell hypoxia—O 2 deficiency. We have used atomistic molecular dynamics simulations at 37°C to investigate the combined influence of headgroup and cholesterol on oxygen permeability in double-component bilayer systems. Relative to the oxygen permeability of PC(16:0/18:1) or POPC at 16.5 ± 0.6 cm/s, exchanging the headgroup with PE or introducing 50 mol% cholesterol gives a drop in permeability to ~12cm/s. Increasing the saturated chain length to 18:0 gives a permeability of 10 to 11 cm/s, regardless of the presence or absence of cholesterol at 50 mol%. Among bilayer physical properties, the best established predictor of membrane permeability for a given solute is area-per-lipid, an indicator of lipid lateral packing density. Our findings are consistent with the dominance of area per lipid as a determinant of oxygen permeability, though cholesterol complicates the analysis somewhat. In particular, cholesterol increases the lateral packing density of PC lipids but cannot further increase the tightness of packing (or reduce the permeability) for PE lipids. Further, the longer 18:0 saturated tail reduces the area-per-lipid and the oxygen permeability, relative to the 16:0 tail, diminishing the effect of the smaller PE headgroup.

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