TY - JOUR

T1 - The Gaussian curvature elastic modulus of N-monomethylated dioleoylphosphatidylethanolamine

T2 - Relevance to membrane fusion and lipid phase behavior

AU - Siegel, David Paul

AU - Kozlov, M. M.

N1 - Funding Information:
M.M.K. thanks the Human Frontier Science Program Organization, the Israel Science Foundation (grant 75/03), and the Binational USA-Israel Science Foundation for financial support.

PY - 2004/7

Y1 - 2004/7

N2 - The energy of intermediates in fusion of phospholipid bilayers is sensitive to κm, the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value κm is also important in understanding the stability of inverted cubic (Q∥) and rhombohedral (R) phases relative to the lamellar (Lα) and inverted-hexagonal (H∥) phases in phospholipids. However, κm cannot be measured directly. It was previously measured by observing changes in Q∥ 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 κm. At the temperature of the Lα/ ∥ phase transition, TQ, the partial energies of the two phases are equal, and we can express κm in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus κm, and the distance of the monolayer neutral surface from the bilayer midplane, δ. The calculated ratio κm/κm is -0.83 ± 0.08 at TQ ≈ 55°C. The uncertainty is due primarily to uncertainty in the value of δ for the Lα phase. This value of κm/ κm 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 κm substantially affects the free energy of formation of fusion intermediates: more energy (tens of kBT) 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 QII phase stability and Lα/QII 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.

AB - The energy of intermediates in fusion of phospholipid bilayers is sensitive to κm, the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value κm is also important in understanding the stability of inverted cubic (Q∥) and rhombohedral (R) phases relative to the lamellar (Lα) and inverted-hexagonal (H∥) phases in phospholipids. However, κm cannot be measured directly. It was previously measured by observing changes in Q∥ 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 κm. At the temperature of the Lα/ ∥ phase transition, TQ, the partial energies of the two phases are equal, and we can express κm in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus κm, and the distance of the monolayer neutral surface from the bilayer midplane, δ. The calculated ratio κm/κm is -0.83 ± 0.08 at TQ ≈ 55°C. The uncertainty is due primarily to uncertainty in the value of δ for the Lα phase. This value of κm/ κm 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 κm substantially affects the free energy of formation of fusion intermediates: more energy (tens of kBT) 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 QII phase stability and Lα/QII 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.

UR - http://www.scopus.com/inward/record.url?scp=3042776328&partnerID=8YFLogxK

U2 - 10.1529/biophysj.104.040782

DO - 10.1529/biophysj.104.040782

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AN - SCOPUS:3042776328

SN - 0006-3495

VL - 87

SP - 366

EP - 374

JO - Biophysical Journal

JF - Biophysical Journal

IS - 1

ER -