
PI(4,5)P2 is a phospholipid found mostly in the plasma membrane of eukaryotic cells, where it plays a crucial role in processes like vesicle trafficking, cytoskeletal regulation, ion channel function, viral assembly and budding. While most phospholipids show considerable acyl-chain diversity, PI(4,5)P2 lipids are exceptionally enriched in specific acyl-chains, the most frequent composition in mammalian cells being 1-stearoyl-2-arachidonyl (18:0 20:4). The biological functions that call for this specific enrichment are still not fully clear. In a recent paper published in Communications Chemistry, a BSIRG-iBB team led by Fábio Fernandes together with the teams of Dr. Nuno Santos (IMM) and Dr. Manuel Melo (ITQB) identified a previously unreported increase in membrane order upon calcium-dependent PI(4,5)P2 clustering. Remarkably, the interaction of saturated PI(4,5)P2 with calcium culminated in the formation of gel nanodomains for fully saturated PI(4,5)P2, and the formation of these gel domains was abrogated in the presence of 18:0 20:4 polyunsaturated PI(4,5)P2. These results support a role of (18:0 20:4)PI(4,5)P2 in inhibiting the formation of highly ordered PI(4,5)P2 nanodomains in the plasma membrane.