J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 49, 1918-1925, September 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Do unsaturated phosphoinositides mix with ordered phosphadidylcholine model membranes?

Antje Hermelink and Gerald Brezesinski1

Max Planck Institute of Colloids and Interfaces, Research Campus Golm, 14476 Potsdam, Germany

Published, JLR Papers in Press, May 14, 2008.

This work was supported by the Max Planck Society.

1 To whom correspondence should be addressed. e-mail: brezesinski{at}mpikg.mpg.de

Phosphoinositides have been shown to control membrane trafficking events by targeting proteins to specific cellular sites, which requires a tight regulation of phosphoinositide generation and turnover as well as a high degree of compartmentalization. To shed light on the processes that lead to the formation of phosphoinositide-enriched microdomains, mixed monolayers of phosphatidylcholine and dioleoyl-phosphatidylinositol (DOPtdIns) or dioleoyl-phosphatidylinositol-bisphosphate [DOPtdIns(4,5)P2] were investigated by isothermal area/pressure measurements, Brewster angle microscopy, and grazing incidence X-ray diffraction. The results are consistent with a charge-dependent formation of phosphatidylinositol-containing tightly packed phases. DOPtdIns is capable of mixing partially with condensed 1,2-distearoyl-phosphatidylcholine (DSPC) and of forming mixed crystals that differ significantly from those formed by pure DSPC. DOPtdIns(4,5)P2 in mixtures with DSPC is, to a much larger extent, phase separated. The observed phase separation of the highly charged DOPtdIns(4,5)P2 is presumably water stabilized by electrostatic interactions and hydrogen bonding. In biological systems, an enzymatic phosphorylation of phosphatidylinositol in mixed domains may cause their insolubility in ordered phosphatidylcholine areas and lead to a cooperative reorganization of the host lipid membrane. This strong cooperative effect underlines the important role of PtdIns(4,5)P2 in signal transduction processes and suggests that the ability of phosphoinositides to induce or reduce long-range interactions in phospholipid mixtures is crucial.

Supplementary key words DOPtdIns • DOPtdIns(4,5)P2 • 1,2-distearoyl-phosphatidylcholine • phase separation • hydrogen bonding • monolayer structure


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