Abstract 159: Eicosapentaenoic Acid and Docosahexaenoic Acid Have Distinct Membrane Locations and Lipid Interactions as Determined by X-ray Diffraction

Abstract

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differentially influence lipid oxidation, signal transduction, fluidity, and cholesterol domain formation, potentially due to distinct membrane interactions. We used small angle x-ray diffraction to test EPA and DHA effects on model membrane structure. Vesicles were prepared to model human peripheral cell membranes using 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) and cholesterol (C) (0.3 C:POPC mole ratio), and treated with vehicle, EPA, or DHA (1:10 mole ratio to POPC). Membrane width ( d- space) was 59.5 Å at 10°C, decreasing to 54.7 Å at 30°C due to increased acyl chain dynamics. EPA or DHA had no effect on membrane d -space (<1 Å change). Electron density profiles from diffraction data were superimposed on corresponding vehicle profiles (Fig. 1). EPA increased membrane hydrocarbon core electron density over a broad area, up to ± 20 Å from the membrane center, indicating an energetically favorable extended membrane orientation for EPA, stabilized by van der Waals interactions. By contrast, DHA increased electron density in the phospholipid head group region starting at ± 12 Å from the membrane center, due to DHA-surface interactions, resulting in a pronounced electron density reduction and increased disorder in the membrane hydrocarbon core centered ± 7-9 Å from the membrane center. DHA disordering effects were less apparent at higher temperatures, likely due to greater rotational dynamics, while EPA effects were stable. The contrasting EPA and DHA effects on membrane structure signify distinct molecular locations/orientations and may contribute to observed differences in biological activity.