Measurement of the membrane curvature preference of phospholipids reveals only weak coupling between lipid shape and leaflet curvature
Measurement of the membrane curvature preference of phospholipids reveals only weak coupling between lipid shape and leaflet curvature
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DOI：
10.1073/pnas.0907354106
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发表时间：
2009-12-29
影响因子：
11.1
通讯作者：
Howard, Jonathon
中科院分区：
文献类型：
--
作者：
Kamal, Marzuk M.;Mills, Deryck;Howard, Jonathon
在生物过程中，如裂变、融合和运输，已经表明不同形状的脂质被分选到具有不同膜曲率的区域中。这种脂质分选被假设是由于膜曲率和脂质的自发曲率之间的耦合，这与脂质的分子形状有关。另一方面，理论预测和模拟表明，脂质的曲率偏好，由于形状本身，比在生物过程中观察到的要弱。为了区分这些不同的观点，我们通过使用基于荧光的方法直接测量了几种脂质的曲率偏好。我们制备了不同大小的小单层囊泡与混合物的蛋-PC和小摩尔分数的N-硝基苯并恶二唑（NBD）标记的磷脂或溶血磷脂的不同链长和饱和度和测量的NBD平衡分布在整个双层。我们观察到横向脂质分布线性依赖于膜曲率，使我们能够测量曲率耦合系数。我们的测量是在定量协议与预测的基础上较早的测量相应的非荧光脂质使用X-射线衍射的自发曲率。我们发现，虽然一些脂质具有较高的自发曲率，但由于脂质分子面积的低值，它们仍然表现出较弱的曲率偏好。弱曲率偏好意味着在生物膜中发现的不对称脂质分布不太可能由脂质的自发曲率驱动，也不是脂质区分膜曲率的传感器。
In biological processes, such as fission, fusion and trafficking, it has been shown that lipids of different shapes are sorted into regions with different membrane curvatures. This lipid sorting has been hypothesized to be due to the coupling between the membrane curvature and the lipid's spontaneous curvature, which is related to the lipid's molecular shape. On the other hand, theoretical predictions and simulations suggest that the curvature preference of lipids, due to shape alone, is weaker than that observed in biological processes. To distinguish between these different views, we have directly measured the curvature preferences of several lipid by using a fluorescence-based method. We prepared small unilamellar vesicles of different sizes with a mixture of egg-PC and a small mole fraction of N-nitrobenzoxadiazole (NBD)-labeled phospholipids or lysophospholipids of different chain lengths and saturation and measured the NBD equilibrium distribution across the bilayer. We observed that the transverse lipid distributions depended linearly on membrane curvature, allowing us to measure the curvature coupling coefficient. Our measurements are in quantitative agreement with predictions based on earlier measurements of the spontaneous curvatures of the corresponding nonfluorescent lipids using X-ray diffraction. We show that, though some lipids have high spontaneous curvatures, they nevertheless showed weak curvature preferences because of the low values of the lipid molecular areas. The weak curvature preference implies that the asymmetric lipid distributions found in biological membranes are not likely to be driven by the spontaneous curvature of the lipids, nor are lipids discriminating sensors of membrane curvature.