Biophysical Society Thematic Meeting - October 13-15, 2015

Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling

Poster Abstracts

15-POS Board 15 Edelfosine Shows Affinity for Cholesterol and Disorganizes Liquid Ordered Structures Juan Gomez-Fernandez , Pablo Hernández-Valera, Monika Schneider, Victoria Gomez-Murcia, Ana M. DeGodos, Alejandro Torrecillas, Senena Corbalan-Garcia. University of Murcia, Murcia, Spain. Edelfosine is an alkl-lysophospholipid with antineoplastic and immunomodulating effects. We compare here the effect of edelfosine on the organization, at different temperatures, of liquid ordered membrane-like structures, with four other asymmetric phospholipids, PAF, PAPC, lysoPAF and lysoPC. When a POPC/SM/cholesterol (1:1:1 mole ratio) ternary mixture was studied by DSC no phase transition was detected, but the addition of 20 mol % edelfosine to produced a phase transition Lβ to Lα. This new transition should be attributed to the association of edelfosine to cholesterol capable of neutralizing its effect. Such a transition was not produced by the addition of the other four asymmetric phospholipids. Results from SAXD showed that edelfosine, PAF and PAPC at 5 and 15°C produced spacings that suggest lamellar crystalline structure, while at 45°C results indicated a bilayer structure in fluid state. In contrast, lysoPC produces a crystalline structure at 5 and 15°C, while at 45°C was in a bilayer in fluid state. Furthermore, the spacing of the sample with lysoPAF at 5°C indicates that it has two phases, probably both of lamellar type. At 15°C the pattern displays a spacing indicating that one of the two phases disappeared, while at 45°C two spacings indicate that the lamellar phase that remains is a bilayer in fluid state. 31P-NMR showed that edelfosine forms bilayers when combined with just cholesterol, being more capable of doing so than the other compounds studied. These bilayers were characterized by microscopy. The results obtained in this study support the theory that the antitumor drug edelfosine acts through reorganization and modification of lipid rafts in liquid ordered state (Lo) and therefore supports that these domains are a promising therapeutic target against cancer.

78