Interactions of valproic acid with lipid membranes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine

Abstract

Lipid bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were prepared in two forms, as a suspension of multilamellar spherical vesicles and as planar membranes deposited on a conductive solid support. We used Fourier Transformed Infrared (FTIR) and Raman spectroscopic techniques to study the lipid vesicles while the solid supported bilayers were characterized by using electrochemical experiments (cyclic voltammetry and impedance). Valproic acid (Valp) was either present in the solution or incorporated into the lipid structure. As the Valp:DMPC ratio increases the phase transition temperature decreases while the phase transition becomes less marked. Moreover, for the Valp:DMPC complex species a slight decrease in the number of gauche isomers was observed relative to the number of trans isomers what corresponds to an increase in the packing density of the acylic chains. Based on derived electrical properties of the supported membranes it can be concluded that Valp induces the formation of pores and other defects in the lipid films. Valp incorporated into the membrane is seriously detrimental to the bilayer stability.