title: The gaussian curvature elastic modulus of N-monomethylated dioleoylphosphatidylethanolamine: relevance to membrane fusion and lipid phase behavior.
abstract: The energy of intermediates in fusion of phospholipid bilayers is sensitive to kappa(m), the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value kappa(m) is also important in understanding the stability of inverted cubic (Q(II)) and rhombohedral (R) phases relative to the lamellar (L(alpha)) and inverted hexagonal (H(II)) phases in phospholipids. However, kappa(m) cannot be measured directly. It was previously measured by observing changes in Q(II) phase lattice dimensions as a function of water content. Here we use observations of the phase behavior of N-mono-methylated dioleoylphosphatidylethanolamine (DOPE-Me) to determine kappa(m). At the temperature of the L(alpha)/Q(II) phase transition, T(Q), the partial energies of the two phases are equal, and we can express kappa(m) in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus kappa(m), and the distance of the monolayer neutral surface from the bilayer midplane, delta. The calculated ratio kappa(m)/kappa(m) is -0.83 +/- 0.08 at T(Q) approximately 55 degrees C. The uncertainty is due primarily to uncertainty in the value of delta for the L(alpha) phase. This value of kappa(m)/kappa(m) is in accord with theoretical expectations, including recent estimates of the value required to rationalize observations of rhombohedral (R) phase stability in phospholipids. The value kappa(m) substantially affects the free energy of formation of fusion intermediates: more energy (tens of k(B)T) is required to form stalks and fusion pores (ILAs) than estimated solely on the basis of the bending elastic energy. In particular, ILAs are much higher in energy than previously estimated. This rationalizes the action of fusion-catalyzing proteins in stabilizing nascent fusion pores in biomembranes; a function inferred from recent experiments in viral systems. These results change predictions of earlier work on ILA and Q(II) phase stability and L(alpha)/Q(II) phase transition mechanisms. To our knowledge, this is the first determination of the saddle splay (Gaussian) modulus in a lipid system consisting only of phospholipids.
authors.affiliation: Givaudan, Inc., Cincinnati, Ohio 45216, USA. david.siegel@givaudan.com
authors.forename: D P
authors.initials: DP
authors.lastname: Siegel
authors.forename: M M
authors.initials: MM
authors.lastname: Kozlov
mesh_terms: D000465:Algorithms; D008561:Membrane Fusion; D008962:Models, Theoretical; D044367:Phase Transition; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D013696:Temperature
chemical_list: D010714:Phosphatidylethanolamines; D010743:Phospholipids; C094877:dioleoyl phosphatidylethanolamine