Comparative Characteristics of Membrane-Active Single-Chained Ether Phospholipids: PAF and Lyso-PAF in Langmuir Monolayers

Abstract

1-O-Octadecyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and its deacetylated precursor (lyso-PAF) are membrane-active single-chained ether phospholipids, which play an important signaling role in different physiological processes. There is strong evidence that one of the possible mechanisms of PAF and lyso-PAF activity is connected with their direct influence on biomembranes. Although both lipids have very similar structure, their biological activity is very different and in some cases even antagonistic. Unfortunately, there is a lack of the studies correlating these observations with the molecular structure of both compounds. Therefore, we decided to apply model systems and advanced physicochemical methods to explore this subject and look for the reasons of the observed discrepancies. As a model system, we prepared Langmuir monolayers of PAF and lyso-PAF at the air/water interface. The physicochemical characteristic of the model membranes under different experimental conditions was performed with the application of the Langmuir monolayer technique, Brewster angle microscopy, and the methods based on synchrotron radiation scattering (XR and GIXD). Both compounds form stable Langmuir monolayers, in which the lipid molecules are strongly immersed into the water subphase. The monolayers have expanded character, meaning that the hydrophobic tails are considerably tilted and disordered. Similarly to biochemical studies, also in our model systems, profound differences in the properties of PAF and lyso-PAF were observed. Contrary to PAF, the lyso-PAF molecules express the propensity to form organized, periodical structures in the model membranes. It is manifested in the phase transition observed in the course of the lyso-PAF π-A isotherm which was correlated with the diffraction signal registered with the application of the GIXD method. The formation of 2D domains of hexagonal ordering of the film forming molecules was observed only for the lyso precursor. The observed differences between PAF and lyso-PAF were explained taking into consideration the chemical activity of the free hydroxyl group present in the headgroup of the latter molecule. The formation of hydrogen bonds between the lyso-PAF molecules as well as the stronger hydration of its hydrophilic fragment can be the key factor differentiating the activity of PAF and lyso-PAF in the investigated systems as well as in the native biomembranes.