Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Diacylglycerols (DAGs) with unsaturated acyl chains play many important roles in biomembranes, such as a second messenger and activator for protein kinase C. In this study, three DAGs of distinctly different chain unsaturations (i.e. di16:0DAG (DPG), 16:0-18:1DAG (POG), and di18:1DAG (DOG)) are studied using atomistic MD simulation to compare their roles in the structure and dynamics of 16:0-18:1phosphatidylcholine (POPC) membranes. All three DAGs are able to produce the so-called 'condensing effect' in POPC membranes: decreasing area-per-lipid, and increasing acyl chain order and bilayer thickness. Our visual and quantitative analyses clearly show that DAG with unsaturated chains induce larger spacing between POPC headgroups, compared with DAG with saturated chains; this particular effect has long been hypothesized to be crucial for activating enzymes and receptors in cell membranes. DAGs with unsaturated chains are also located closer to the bilayer/aqueous interface than DPG and are more effective in slowing down lateral diffusion of molecules. We show that DAG molecules seek the "umbrella coverage" from neighboring phospholipid headgroups - similar to cholesterol. Unlike cholesterol, DAGs also hide their chains from water by laterally inserting their chains into the surrounding. Thus, acyl chains of DAG are more spread and disordered than those of PC due to the insertion. By calculating the potential of mean force (PMF) for POPC in POPC/DAG bilayers, we found that all three DAGs can significantly increase the free energy barrier for POPC to flip-flop, but only DAGs with unsaturated chains can additionally increase the free energy of POPC desorption.