The biophysical properties of ethanolamine plasmalogens revealed by atomistic molecular dynamics simulations

Photo by vjanez/iStock / Getty Images

Rog T and Koivuniemi A. (2016) The biophysical properties of ethanolamine plasmalogens revealed by atomistic molecular dynamics simulations. Biochimica et Biophysica Acta

Plasmalogens are a class of lipids containing a vinyl-ether bond at sn-1, resulting in a compact structure and providing the lipids with unique characteristics. It is known that plasmalogens have roles in membrane structure, vesicular fusion, and protecting against oxidative stress. A reduction in plasmalogen levels has been associated with many disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and autism spectrum disorders. This association lends support for the biological importance of plasmalogens. Prior to 2016, the basic biophysical characteristics of plasmalogens were known, but most of the molecular details behind them had not been elucidated. Rog and Koivuniemi wanted to delve further into the molecular properties of ethanolamine plasmalogens and in particular the role of the vinyl-ether bond. To determine the importance of the vinyl-ether bond, atomistic molecular dynamics was used to compare three simulated bilayers containing either ethanolamine plasmalogens (PlsEtn), phosphotidylcholine (PtdCho), or phosphotidylethanolamine (PtdEtn). The latter two are also common cell membrane lipids and were chosen to compare PlsEtn because PtdCho is found in the greatest amounts in humans and PtdEtn provides a comparison with a lipid containing the same chains as PlsEtn, but lacking the vinyl bond.

Measuring the average distance between phosphorous atoms of the bilayer leaflets enabled the thickness to be determined and compared. It was observed that bilayers made up of PlsEtns are thicker and more compact than those composed of PtdEtn and PtdCho at 4.4 nm, 4.2 nm, and 3.7 nm, respectively. The vinyl bond appears to increase thickness by 0.2 nm, but the greatest thickness determinant based on these findings is the ethanolamine headgroup as PlsEtn and PtdEtn are closer in size, but also much greater than PtdCho.

To further determine how condensed the different bilayers are, the area per lipid was calculated by dividing the bilayer area by the number of lipids in one leaflet. When compared, the PlsEtn bilayer had the lowest area per lipid at 0.53 nm^2 while PtdEtn and PtdCho had areas of 58 nm^2 and 68 nm^2, respectively. These findings indicate that PlsEtn lipids are aligned more closely together and that the vinyl bond is necessary to reduce the area. In addition, it was confirmed that the sn-1 and sn-2 chains in the PlsEtn bilayers was more ordered than PtdCho and PtdEtn, agreeing with the historical literature.

Increasing our understanding of the biophysical structure of plasmalogens and how that influences their molecular properties, will allow for the elucidation of how they interact with other lipids, proteins, and compounds. The work by Rog and Koivuniemi has helped to implicate the role of the vinyl-ether bond in the biophysical properties of the membrane. They showed that the vinyl bond is responsible for the condensed nature of a bilayer composed of PlsEtn and that it reduced the leaflet area per lipid. In their discussion, they theorize that plasmalogens likely increase the spontaneous curvature of the bilayer based on the simulated density profiles of the PlsEtn bilayer compared to the PtdCho bilayer. A greater curvature aides in the bending of membranes, making the membrane more fusogenic. As neurons need to be able to form vesicles and have them fuse to the nerve terminal for neurotransmission to occur, it is unsurprising that plasmalogens are enriched in neuronal membranes. Neurodegenerative disorders have been associated with reduced levels of plasmalogens and work like this has provided clues to the molecular explanation behind the physiological roles of plasmalogens in the pathology of these neurological disorders.