Effect of Phosphatidylinositol-Bisphosphate (PIP2) Lipids on Membrane Structure and Forces

It is widely accepted that the interaction between lipid bilayers at closest separation is dominated by a repulsive hydration force arising from the structuring of water molecules on the lipid bilayer surface. This force has been recognized as a major activation energy barrier preventing fusion of bilayers. Our working hypothesis is that the orientation of the hydrogen bond network on the bilayer surface determines the amplitude of the hydration force. We are testing this hypothesis using the 1,2-dioleoyl-sn-glycero-3-phospho-[1′-myo-inositol-4’,5′-bisphosphate](PI(4,5)P2) lipid and its isomers which differ in the position of phosphate groups on the inositol ring. Phosphatidylinositol-bisphosphate (PIP2) lipids are pivotal in signaling and play an important role in exocytosis. Specifically, we have utilized small angle X-ray diffraction (SAXS) and monitored the structural consequences of osmotic pressure in multilamellar suspensions of dioleoylphosphatidylcholine (DOPC) in the presence of PI(4,5)P2. Our preliminary data (powder X-ray diffraction and reconstructed electron density profiles) show that there are notable changes in bilayer structure, particularly the lamellar repeat distance, thickness, and forces in the presence of PI(4,5)P2. We are currently investigating whether the effects of PIP2 lipids are dependent on the phosphate group position, ionic strength, and temperature. Since the relative position of the hydrogen bond acceptor in phosphates are determined by their exact molecular structure, our results will be relevant in the context of molecular recognition involving PIP2 lipids.