Sphingosine and sphingosine-1-phosphate (S1P) are known as signaling lipids which are produced from ceramide as follows: Ceramide↔Sphingosine↔S1P.
The ratio between these three lipids determines cell fate. In the framework of this “sphingolipid rheostat”, increased level of sphingosine or ceramide promotes apoptosis, while increased S1P leads to proliferation. Although their direct interaction with signaling proteins is important, their effect on membrane physical properties might also play a role. Sphingosine and S1P are single chain lipids bearing positive and negative charge respectively at physiological pH. Our motivation is finding clues to explain the mechanisms of "sphingosine rheostat" from a physicochemical viewpoint by using artificial membranes.
Large unilamellar vesicles made of egg phosphatidylcholine were used to study the sphingosine and S1P effect on (i) electrostatic properties by zeta potential measurement and (ii) membrane packing by fluorescence generalized polarization (GP) measurement using LAURDAN. First, we studied the sphingosine and S1P effects separately. GP measurement revealed that an increase of sphingosine content made the membrane more packed, while S1P had few effects on packing. Sphingosine and S1P had opposite effect on zeta potential leading to positive and more negative values respectively. This allowed us to tune the zeta potential linearly from positive to negative value, through blending the two lipids. Unlike for zeta potential, the simultaneous effect of sphingosine and S1P on lipid packing was synergistic. This shows the existence of a sphingosine-S1P cooperative effect on membrane structuring. A parallel study using giant unilamellar vesicles revealed the corresponding lipid membrane phase behaviour.
The observation that modification of the sphingosine/S1P ratio tunes both membrane charge and membrane packing might support the idea that the antagonistic role of both lipids in cell life is due in part to their effect on lipid bilayer physical properties.
miglena.anguelova@upmc.fr
