Solute-induced acceleration of transbilayer movement and its implications on models of blood-brain barrier

Hexylglycerol accelerates the transbilayer (flip-flop) movement of phospholipids, lysophospholipids and peptides. For example, lysophosphatidylcholine added to dimyristoylphosphatidylcholine vesicles activates the action of pig pancreatic phospholipase A2 (Jain and DeHaas (1983) Biochim. Biophys. Acta 736, 157-162) This activating effect is dissipated slowly after mixing, and no activation is observed when the lysophospholipid molecules are equally distributed on both sides of the bilayer. The half time for transbilayer movement of lysophosphatidylcholine is about 7 h, and it is accelerated over 100-fold in the presence of n-hexylglycerol, as well as by a variety of other amphipathic solutes including n-alkanols, ketamine, and flufenamic acid. Hexylglycerol also accelerates the rate of transbilayer movement of an amphipathic hexapeptide bocLALALW, as well as of the phosphatidylcholine molecules in erythrocyte membrane. These effects are observed without any change in the gross bilayer organization as judged by 31P-NMR. Biophysical significance of such solute induced acceleration of transbilayer movement of amphipathic solutes is discussed to account for the effect of alkylglycerols on blood brain barrier.