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Sphingosine Increases the Permeability of Model and Cell Membranes

Unidad de Biofísica (Centro Mixto CSIC-UPV/EHU), and Departamento de Bioquímica, Universidad del País Vasco, 48080 Bilbao, Spain

Correspondence: Address reprint requests to Félix M. Goñi, Tel.: 34-94-601-26-25; Fax: 34-94-601-33-60; E-mail: gbpgourf{at}lg.ehu.es.

Sphingosine, at 5–15 mol % total lipids, remarkably increases the permeability to aqueous solutes of liposomal and erythrocyte ghost membranes. The increased permeability cannot be interpreted in terms of leakage occurring at the early stages of a putative membrane solubilization by sphingosine, nor is it due to a sphingosine-induced generation of nonlamellar structures, or flip-flop lipid movement. Instead, sphingosine stabilizes (rigidifies) gel domains in membranes, raising their melting temperatures and increasing the transition cooperativity. Structural defects originating during the lateral phase separation of the "more rigid" and "less rigid" domains are likely sites for the leakage of aqueous solutes to the extravesicular medium. The presence of coexisting domains in the plasma membrane makes it a target for sphingosine permeabilization. The sphingosine-induced increase in rigidity and breakdown of the plasma membrane permeability barrier could be responsible for some of the physiological effects of sphingosine.