Acyl-chain saturation regulates the order of phosphatidylinositol 4,5-bisphosphate nanodomains.

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ) plays a critical role in the regulation of various plasma membrane processes and signaling pathways in eukaryotes. A significant amount of cellular resources are spent on maintaining the dominant 1-stearoyl-2-arachidonyl PI(4,5)P 2 acyl-chain composition, while less abundant and more saturated species become more prevalent in response to specific stimuli, stress or aging. Here, we report the impact of acyl-chain structure on the biophysical properties of cation-induced PI(4,5)P 2 nanodomains. PI(4,5)P 2 species with increasing levels of acyl-chain saturation cluster in progressively more ordered nanodomains, culminating in the formation of gel-like nanodomains for fully saturated species. The formation of these gel-like domains was largely abrogated in the presence of 1-stearoyl-2-arachidonyl PI(4,5)P 2. This is, to the best of our knowledge, the first report of the impact of PI(4,5)P 2 acyl-chain composition on cation-dependent nanodomain ordering, and provides important clues to the motives behind the enrichment of PI(4,5)P 2 with polyunsaturated acyl-chains. We also show how Ca 2+ -induced PI(4,5)P 2 nanodomains are able to generate local negative curvature, a phenomenon likely to play a role in membrane remodeling events.