A unique rapid flip-flop of the naturally occurring negatively charged phospholipid phosphatidylethanol in sonicated phosphatidylcholine vesicles was studied using 13C NMR and phosphatidylethanol 13C-labeled at the CH2 ethyl moiety. The transbilayer diffusion of phosphatidylethanol was observed in response to the formation of Nernst potential (t 1/2 < 7 min), indicating that phosphatidylethanol transfer occurs in the anionic form. The application of the fluorescent potential-sensitive dye di-4-ANEPPS showed that the phosphatidylethanol movement across the membrane was accompanied by a decrease in the Nernst potential. In biological membranes, a facile spontaneous diffusion of phosphatidylethanol implies the lack of high asymmetry of its distribution, even if phosphatidylethanol is synthesized exclusively on one side of the membrane.

Nernst potential drives the fast transmembrane diffusion of anionic phospholipid phosphatidylethanol, indicating low asymmetry in its distribution in biological membranes.

[Nernst potential as a driving force of the fast transmembrane diffusion (flip-flop) of the anionic natural phospholipid phosphatidylethanol].

Key Takeaway: Nernst potential drives the fast transmembrane diffusion of anionic phospholipid phosphatidylethanol, indicating low asymmetry in its distribution in biological membranes.