Effect of psychosine on model lipid membranes

YENISLEIDY DE LAS MERCEDES ZULUETA DIAZ; SOFÍA CABY; ERNESTO BONGARZONE; MARIA LAURA FANANI

Castellón

Congreso; 6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics; 2018

Sociedad Española de Biofísica (SBE), Sociedad Portuguesa de Biofísica (SPBf) y Federación Latinoamericana de Sociedades Biofísicas (LAFeBS)

Psychosine or β-galactosylsphingosine(PSY) is a toxic intermediate in the biosynthesis of sphingolipids occurring in the lysosome lumen. Its accumulation into the cell has been proposed as responsible for the Krabbe disease.Several evidences propose that this amphiphilic molecule exerts its pathological effect by partitioning into membranes and affecting its function.In this work, we have studied how this cationic lipid affects electrostatic and rheological properties of the membranes. We explored the interaction of PSY with phospholipid membranes at neutral pH in different phase state,used as classical model systems. Additionally, we explored PSY interaction with a complex lipid mixture of phospholipids, sphingolipidsand cholesterol that mimic the lipid composition of myelin. For this purpose, we combined monolayer techniques,Brewster Angle Microscopy and Fluorescence, and Zeta PotentialOur results show that PSY at neutral pH exhibit surface activity, being able to lower the surface tension of water from 72 to 32 mN/m,and a CMC of 38 ± 3 M. This value is 30 times lower than the reported CMC at pH 4 evidencing a more hydrophobic character.PSYshows high sensitivity to the phase state. Partitioning preferentially into expanded phases in phospholipid membranes. This result suggests that PSY may stabilize phase separation; affecting the subtle balance that regulates phase separation in myelin. Furthermore, we observed that PSY alters the surface electrostatic of lipid membranes in a complex manner.Being the Krabbe disease a demyelinating process, our results are relevant to the supramolecular interpretation of the mechanism of biomembrane perturbation by PSY