The Gaussian curvature elastic modulus of N-monomethylated dioleoylphosphatidylethanolamine: Relevance to membrane fusion and lipid phase behavior
The Gaussian curvature elastic modulus of N-monomethylated dioleoylphosphatidylethanolamine: Relevance to membrane fusion and lipid phase behavior
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DOI：
10.1529/biophysj.104.040782
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Kozlov, MM
中科院分区：
文献类型：
--
作者：
Siegel, DP;Kozlov, MM
磷脂双分子层融合中中间体的能量对（κ）/bar（m）敏感;脂质单层的鞍形张开（高斯曲率）弹性模量。在理解磷脂中相对于层状（L-alpha）和倒置六方（H-II）相的倒置立方（Q（II））和菱形（R）相的稳定性时，相对于条形（m）的值（κ）也很重要。然而，（κ）除以bar（m）不能直接测量。它以前通过观察作为水含量的函数的Q（II）相晶格尺寸的变化来测量。在这里，我们使用N-单甲基化二油酰磷脂酰乙醇胺（DOPE-Me）的相行为的观察来确定（κ）相对于bar（m）。在L-alpha/Q（II）相变的温度T-Q，两相的分能相等，我们可以用已知的脂质单层参数来表示（κ）/bar（m）：DOPE-Me的自发曲率，单层弯曲模量km和单层中性表面与双层中平面的距离δ。在接近55 ℃的T-Q下，计算出的比（κ）/bar（m）/kappa（m）为-0.83 +/-0.08。不确定性主要是由于L α相位的δ值的不确定性。（κ）/bar（m）/kappa（m）的值与理论预期值雅阁，包括最近对磷脂中菱面体（R）相稳定性观察结果合理化所需值的估计。值（κ）除以bar（m）显著影响形成融合中间体的自由能：形成茎和融合孔（ILA）所需的能量（数十k（B）T）比仅基于弯曲弹性能估计的能量多。特别是，ILA的能量比以前估计的要高得多。这使融合催化蛋白在稳定生物膜中新生融合孔中的作用合理化;这是从最近的病毒系统实验中推断的功能。这些结果改变了对ILA和Q（II）相稳定性和L-alpha/Q（II）相变机制的早期工作的预测。据我们所知，这是第一次确定的鞍展（高斯）模量的脂质系统仅由磷脂。
The energy of intermediates in fusion of phospholipid bilayers is sensitive to (κ) over bar (m); the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value (κ) over bar (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, (κ) over bar (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 (κ) over bar (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 (κ) over bar (m) in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus km, and the distance of the monolayer neutral surface from the bilayer midplane, delta. The calculated ratio (κ) over bar (m)/kappa(m) is -0.83 +/- 0.08 at T-Q approximate to 55degreesC. The uncertainty is due primarily to uncertainty in the value of delta for the Lalpha phase. This value of (κ) over bar (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 (κ) over bar (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.