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Biophys J, December 2000, p. 3193-3200, Vol. 79, No. 6

Electrostatic Control of Phospholipid Polymorphism

Yury S. Tarahovsky,*dagger A. Larry Arsenault,Dagger Robert C. MacDonald,* Thomas J. McIntosh,§ and Richard M. Epanddagger

 *Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208 USA;  dagger Department of Biochemistry and  Dagger Electron Microscopy Facility, Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8N 3Z5 Canada; and  §Department of Cell Biology, Duke University, Durham, North Carolina 27710 USA

A regular progression of polymorphic phase behavior was observed for mixtures of the anionic phospholipid, cardiolipin, and the cationic phospholipid derivative, 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine. As revealed by freeze-fracture electron microscopy and small-angle x-ray diffraction, whereas the two lipids separately assume only lamellar phases, their mixtures exhibit a symmetrical (depending on charge ratio and not polarity) sequence of nonlamellar phases. The inverted hexagonal phase, HII, formed from equimolar mixtures of the two lipids, i.e., at net charge neutrality (charge ratio (CR(+/-)) = 1:1). When one type of lipid was in significant excess (CR(+/-) = 2:1 or CR(+/-) = 1:2), a bicontinuous cubic structure was observed. These cubic phases were very similar to those sometimes present in cellular organelles that contain cardiolipin. Increasing the excess of cationic or anionic charge to CR(+/-) = 4:1 or CR(+/-) = 1:4 led to the appearance of membrane bilayers with numerous interlamellar contacts, i.e., sponge structures. It is evident that interactions between cationic and anionic moieties can influence the packing of polar heads and hence control polymorphic phase transitions. The facile isothermal, polymorphic interconversion of these lipids may have important biological and technical implications.

Biophys J, December 2000, p. 3193-3200, Vol. 79, No. 6
© 2000 by the Biophysical Society   0006-3495/00/12/3193/08  $2.00


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