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

Abstract

AbstractPhosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) 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)P2 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)P2 nanodomains. PI(4,5)P2 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)P2. This is, to the best of our knowledge, the first report of the impact of PI(4,5)P2 acyl-chain composition on cation-dependent nanodomain ordering, and provides important clues to the motives behind the enrichment of PI(4,5)P2 with polyunsaturated acyl-chains. We also show how Ca2+-induced PI(4,5)P2 nanodomains are able to generate local negative curvature, a phenomenon likely to play a role in membrane remodeling events.