Copyright © by Biophysical Society.
Final full-text version of the paper available at: http://www.biophysj.org/cgi/content/abstract/90/11/4085
Sphingosine, at 5–15 mol % total lipids, remarkably increases the permeability to aqueous solutes of liposomal and
erythrocyte ghostmembranes. 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 flipflop
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 extravesicularmedium. 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.
This work was supported in part by grants from the Spanish Ministerio de
Educación y Ciencia (BMC 2002-00784) and the University of the Basque
Country (00042.310-13552/2001). F.X.C. and J.S. were predoctoral
students supported, respectively, by the Ministerio de Educación y Ciencia
and by the Basque government.
Peer reviewed