Phosphatidylethanolamine (PE) lipids are abundant components of cell membranes in both eukaryotes and prokaryotes. These lipids are involved in regulating protein activity and biological membrane function. Moreover, anomalies in PE lipid concentrations are associated with various diseases. To determine how PE lipids differ from the commonly studied phosphatidylcholine (PC) lipids, we performed a series of experiments on PE bilayers with varying acyl chain unsaturation and cholesterol content. Specifically, we investigated saturated 1,2-dimyristoyl- sn -glycero-3-phosphoethanolamine (DMPE), saturated 1,2-dipalmitoyl- sn -glycero-3-phosphoethanolamine (DPPE) 1 , monounsaturated 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoethanolamine (POPE), and di-monounsaturated 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE). Binary systems with PE and PC were studied with varying amounts of cholesterol using small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and solid-state 2 H NMR spectroscopy to investigate their structural properties and thermotropic phase behavior. Analysis of the SAXS, DSC, and 2 H NMR data were conducted over a range of temperatures to enable full characterization of the bilayer phase behavior, focusing on the lamellar-to-hexagonal transition for DOPE bilayers and the gel-to-fluid transition for POPE and DMPE bilayers. Our studies showed that the addition of cholesterol affects both transitions, implying an important regulatory role in membrane fluidity and curvature preference. These findings establish a baseline for further PE research utilizing these methodologies, which can be expanded to ternary lipid systems. Important future directions are to study how interactions between PE and PC lipids govern material bilayer properties and how PE chain unsaturation impacts the phase diagrams of ternary systems compared to their PC counterparts. Such understanding of the role of lipid head groups, such as PC versus PE, in regulating membrane properties will allow for the direct connection between lipidomics and cellular function, with broad applications in synthetic biology and disease intervention. 1 Molugu, T.R. et al., (2022). Biophys. J. 121, 4205–4220.
Arruda et al. (Sun,) studied this question.