(200c) Effects of Unsaturated Phospholipid Dilinoleoylphosphatidylcholine on Degradation of Phospholipid Vesicles Catalyzed By a Model Phospholipase A2
- Conference: AIChE Annual Meeting
- Year: 2018
- Proceeding: 2018 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Monday, October 29, 2018 - 3:30pm-5:00pm
In this study, dilinoleoylphosphatidylcholin (DLPC) was used as a model unsaturated phospholipid. Its acidic degradation product, linoleic acid (LA), is one of the two essential fatty acids and is important to our inflammatory defenses. Through inclusion of DLPC in the dipalmitoylphosphatidylcholin (DPPC) saturated membranes, the effects of unsaturation on the degradation of giant unilamellar vesicles (GUV) were investigated by recording the vesiclesâ deformation using fluorescence microscopy. The mechanisms of the observed differences in the degradation of the DPPC and DPPC-DLPC GUVs were analyzed by comparing the phase behaviors of a series of DPPC-DLPC monolayers (xDLPC =0, 0.2, 0.4, 0.63, and 1) using a Langmuir trough-coupled fluorescence microscope. The Angstrom-length scale analysis of the interfacial packing structures of these films before and after degradation was conducted using X-ray surface scattering techniques.
We found that inclusion of unsaturated phospholipids in the membranes not only enhanced the sPLA2-induced degradation of vesicles, but also changed the vesicle deformation processes and the productsâ configurations. The higher enzyme activity on DPPC-DLPC GUVs compared to DPPC GUVs resulted from the differing phase behaviors and molecular packing structures of DPPC and DLPC moleculse at the interface. On the other hand, the differing deformation processes and final configurations of DPPC and DPPC-DLPC GUVs were related to the distinct interfacial organization of the acid degradation products of DPPC and DLPC. These study findings advance the understanding of the influence of unsaturated phospholipids on the interaction of phospholipid membranes with sPLA2 at the molecular level. Thus the study sheds light on the roles of sPLA2 in related physiological processes and supports development of a systematic mechanism-based approach for designing lipid-based drug delivery systems.