Analysis of Interfacial Membrane Polarity of Brain-Related Lipids via Flattened Tetrahedron Phase Diagram

Ternary phase diagrams are an important tool in analyzing the interactions between different lipid components in the membrane; however, the maximum analytical capacity of 3 lipids is their primary limitation. Phosphatidylethanolamine (PE) is one of the 4 most abundant lipids in the brain that has its phase characteristics and interactions with the other abundant brain lipids [sphingolipids, phosphatidylcholine (PC), and cholesterol] yet to be extensively analyzed. This study had two primary objectives: first, we examined DOPE (an analog for PE) as an important fourth lipid component that may have unique interactions with other common brain lipids or their analogs. We found that increased DOPE inclusion generally induced disorder in the brain sphingomyelin (bSM) membrane at lower temperatures and slightly induced order at higher temperatures. In the DOPC membrane, increased DOPE inclusion was found to solely induce further order at all temperatures in the measured range. Second, we suggest the usefulness of a "flattened tetrahedron phase diagram" as a preliminary methodological step before the full introduction of a fourth lipid component to future lipid membrane analytical projects. After 4 related ternary diagrams were created for bSM, DOPC, DOPE, and Chol mixtures, the flattened tetrahedron phase diagram was assembled and revealed trends that showed a smooth transition from one ternary diagram into another, emphasizing the usefulness in this extension of the ternary phase diagram for analyzing lipids.