Absence of clustering of phosphatidylinositol-(4,5)-bisphosphate in fluid phosphatidylcholine

Phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P-2] plays a key role in the modulation of actin polymerization and vesicle trafficking. These processes seem to depend on the enrichment of PI(4,5)P-2 in plasma membrane domains. Here, we show that PI(4,5)P-2 does not form domains when in a fluid phosphatidylcholine matrix in the pH range of 4.8 - 8.4. This finding is at variance with the spontaneous segregation of PI(4,5)P-2 to domains as a mechanism for the compartmentalization of PI(4,5)P-2 in the plasma membrane. Water/ bilayer partition of PI(4,5)P-2 is also shown to be dependent on the protonation state of the lipid.