This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.118034v1 94/10/3987    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Siegel, D. P. Articles by Tenchov, B. G. PubMed PubMed Citation Articles by Siegel, D. P. Articles by Tenchov, B. G.

Influence of the Lamellar Phase Unbinding Energy on the Relative Stability of Lamellar and Inverted Cubic Phases

D. P. Siegel ^* and B. G. Tenchov 

^* Givaudan Inc., Cincinnati, Ohio 45216; and Northwestern University, Department of Biochemistry, Molecular Biology and Cell Biology, Evanston, Illinois 60208

Correspondence: Address reprint requests to D. P. Siegel, E-mail: david.siegel{at}givaudan.com.

Based on curvature energy considerations, nonbilayer phase-forming phospholipids in excess water should form stable bicontinuous inverted cubic (Q_II) phases at temperatures between the lamellar (L) and inverted hexagonal (H_II) phase regions. However, the phosphatidylethanolamines (PEs), which are a common class of biomembrane phospholipids, typically display direct L/H_II phase transitions and may form intermediate Q_II phases only after the temperature is cycled repeatedly across the L/H_II phase transition temperature, T_H, or when the H_II phases are cooled from T > T_H. This raises the question of whether models of inverted phase stability, which are based on curvature energy alone, accurately predict the relative free energy of these phases. Here we demonstrate the important role of a noncurvature energy contribution, the unbinding energy of the L phase bilayers, g_u, that serves to stabilize the L phase relative to the nonlamellar phases. The planar L phase bilayers must separate for a Q_II phase to form and it turns out that the work of their unbinding can be larger than the curvature energy reduction on formation of Q_II phase from L at temperatures near the L/Q_II transition temperature (T_Q). Using g_u and elastic constant values typical of unsaturated PEs, we show that g_u is sufficient to make T_Q > T_H for the latter lipids. Such systems would display direct L H_II transitions, and a Q_II phase might only form as a metastable phase upon cooling of the H_II phase. The g_u values for methylated PEs and PE/phosphatidylcholine mixtures are significantly smaller than those for PEs and increase T_Q by only a few degrees, consistent with observations of these systems. This influence of g_u also rationalizes the effect of some aqueous solutes to increase the rate of Q_II formation during temperature cycling of lipid dispersions. Finally, the results are relevant to protocols for determining the Gaussian curvature modulus, which substantially affects the energy of intermediates in membrane fusion and fission. Recently, two such methods were proposed based on measuring T_Q and on measuring Q_II phase unit cell dimensions, respectively. In view of the effect of g_u on T_Q that we describe here, the latter method, which does not depend on the value of g_u, is preferable.