J. Lipid Res.
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A more recent version of this article appeared on March 1, 2005

Papers In Press, published online ahead of print December 16, 2004
J. Lipid Res., doi:10.1194/jlr.M400367-JLR200
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Submitted on September 24, 2004
Revised on December 2, 2004
Accepted on December 7, 2004

pH-dependent domain formation in phosphatidylinositol polyphosphate/phosphatidylcholine mixed vesicles

Duane A. Redfern and Arne Gericke

Chemistry Department, Kent State University, Kent, OH 44240

Corresponding Author: agericke{at}kent.edu

Phosphatidylinositol polyphosphates have been shown to mediate a large variety of physiological processes by attracting proteins to specific cellular sites. Such site-specific signaling requires local accumulation of phosphatidylinositol polyphosphates and in the light of the rich headgroup functionality, it is conceivable that hydrogen bond formation between adjacent headgroups is a contributing factor for the formation of phosphatidylinositol polyphosphate enriched domains. To explore the significance of hydrogen bond formation for the mutual interaction of phosphatidylinositol polyphosphates, this study aims to characterize the pH-dependent phase behavior of phosphatidylcholine/phosphatidylinositol bis- and trisphosphate mixed vesicles by differential scanning calorimetry (DSC), infrared (IR) transmission spectroscopy and fluorescence resonance energy transfer (FRET) measurements. For pH values above 7 – 7.5, the experiments yielded results consistent with dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylinositol polyphosphate gel phase demixing, while for moderately acidic conditions an enhanced mixing was observed. Similarly, this pH-dependent formation of phosphatidylinositol polyphosphate enriched domains was also found for the physiologically important fluid phase. The stability of phosphatidylinositol polyphosphate enriched domains and to some extent the pH dependence of the domain formation was governed by the number as well as by the position of the phosphomonoester groups at the inositol ring.


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