Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity

P Campomanes and V Zoni and S Vanni, COMMUNICATIONS CHEMISTRY, 2, 72 (2019).

DOI: 10.1038/s42004-019-0175-7

Diacylglycerols (DAGs) are bioactive lipids that are ubiquitously present at low concentrations in cellular membranes. Upon the activation of lipid remodeling enzymes such as phospholipase C and phosphatidic acid phosphatase, DAG concentration increases, leading to a disruption of the lamellar phase of lipid membranes. To investigate the structural origin of these phenomena, here we develop a coarse-grained model for DAGs that is able to correctly reproduce its physicochemical properties, including interfacial tension and flip-flop rate. We find that even at low concentrations a nonnegligible percentage of DAG molecules occupies the interleaflet space. At high concentrations, DAG molecules undergo a phase-separation process from lamellar lipids, segregating in DAG-only blisters and effectively reducing the DAG surface pool available to peripheral enzymes. Our results allow for a better understanding of the role of DAGs in cellular membranes and provide a new tool for the quantitative estimation of low-abundance lipids on membrane properties.

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