The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion
The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion
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DOI：
10.1016/s0006-3495(99)77197-3
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发表时间：
1999-01-01
影响因子：
3.4
通讯作者：
Siegel, DP
中科院分区：
文献类型：
--
作者：
Siegel, DP
脂质组装体的能量学模型（Siegel. 1993. Biophys. J. 65：2124-2140）用于预测层状（L-alpha）反六方（H-平行于）和反立方（Q（平行于））相之间的转变中的中间体的相对自由能。该模型以前被用来产生膜融合的修改后的茎理论。修正的茎理论提出，最低的能量结构之间形成的并列膜的茎和transmonolayer接触（TMC），分别。L-alpha/H-平行和L-alpha/Q（平行）相变的第一步也是膜间事件：L-alpha相的双层必须相互作用，以形成新的拓扑结构。因此，在这些相变的中间体应该是类似的中间体在修改后的茎机制的融合。这里的计算表明，茎和TMC可以介导L-α，Q（平行于）和H-平行于相位之间的转变。这些预测得到了通过时间分辨低温电子显微镜研究这些转变机制的支持（Siegel等人，1994年）。Biophys. J. 66：402-414; Siegel and Epand. 1997. Biophys. J. 73：3089-3111），而以前提出的过渡机制的预测不是。该模型还预测，Q（平行）相应该是热致性脂质系统中的稳定。在某些磷脂系统中，L-alpha/Q（平行于）跃迁的显著滞后可能是由于脂质组成依赖性效应，而不是脂质自发曲率的差异。相关的组成依赖性的性质是高斯曲率模量和膜破裂张力，这可能会改变TMCs的稳定性。TMC的稳定性也影响并置双层的膜融合速率，因此这两个性质也可能影响模型膜和生物膜系统中的融合速率。蛋白质催化膜融合的一种方式可能是通过使这些脂质性质发生局部变化。最后，虽然该模型确定秸秆和TMC作为最低能量的膜间中间体在融合和层状/反转相变，本模型计算的秸秆和TMC的能量仍然很大。这表明，目前的中间体或中间能量模型存在缺陷。这些缺陷的可能性质进行了讨论。
A model of the energetics of lipid assemblies (Siegel. 1993. Biophys. J. 65:2124-2140) is used to predict the relative free energy of intermediates in the transitions between lamellar (L-alpha) inverted hexagonal (H-parallel to), and inverted cubic (Q(parallel to)) phases. The model was previously used to generate the modified stalk theory of membrane fusion. The modified stalk theory proposes that the lowest energy structures to form between apposed membranes are the stalk and the transmonolayer contact (TMC), respectively. The first steps in the L-alpha/H-parallel to and L-alpha/Q(parallel to) phase transitions are also intermembrane events: bilayers of the L-alpha phase must interact to form new topologies during these transitions. Hence the intermediates in these phase transitions should be similar to the intermediates in the modified stalk mechanism of fusion. The calculations here show that stalks and TMCs can mediate transitions between the L-alpha, Q(parallel to), and H-parallel to phases. These predictions are supported by studies of the mechanism of these transitions via time-resolved cryoelectron microscopy (Siegel et al. 1994. Biophys. J. 66:402-414; Siegel and Epand. 1997. Biophys. J. 73:3089-3111), whereas the predictions of previously proposed transition mechanisms are not. The model also predicts that Q(parallel to) phases should be thermodynamically stable in all thermotropic lipid systems. The profound hysteresis in L-alpha/Q(parallel to) transitions in some phospholipid systems may be due to lipid composition-dependent effects other than differences in lipid spontaneous curvature. The relevant composition-dependent properties are the Gaussian curvature modulus and the membrane rupture tension, which could Change the stability of TMCs. TMC stability also influences the rate of membrane fusion of apposed bilayers, so these two properties may also affect the fusion rate in model membrane and biomembrane systems. One way proteins catalyze membrane fusion may be by making local changes in these lipid properties. Finally, although the model identifies stalks and TMCs as the lowest energy intermembrane intermediates in fusion and lamellar/inverted phase transitions, the stalk and TMC energies calculated by the present model are still large. This suggests that there are deficiencies in the current model for intermediates or intermediate energies. The possible nature of these deficiencies is discussed.