Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany.
Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
Proc Natl Acad Sci U S A. 2018 May 29;115(22):5756-5761. doi: 10.1073/pnas.1722320115. Epub 2018 May 14.
The ganglioside GM1 is present in neuronal membranes at elevated concentrations with an asymmetric spatial distribution. It is known to generate curvature and can be expected to strongly influence the neuron morphology. To elucidate these effects, we prepared giant vesicles with GM1 predominantly present in one leaflet of the membrane, mimicking the asymmetric GM1 distribution in neuronal membranes. Based on pulling inward and outward tubes, we developed a technique that allowed the direct measurement of the membrane spontaneous curvature. Using vesicle electroporation and fluorescence intensity analysis, we were able to quantify the GM1 asymmetry across the membrane and to subsequently estimate the local curvature generated by the molecule in the bilayer. Molecular-dynamics simulations confirm the experimentally determined dependence of the membrane spontaneous curvature as a function of GM1 asymmetry. GM1 plays a crucial role in connection with receptor proteins. Our results on curvature generation of GM1 point to an additional important role of this ganglioside, namely in shaping neuronal membranes.
神经节苷脂 GM1 在神经元膜中以不对称的空间分布形式存在于较高浓度下。已知 GM1 能够产生曲率,并且可以预期其会强烈影响神经元形态。为了阐明这些影响,我们制备了 GM1 主要存在于膜的一个叶中的巨大囊泡,模拟神经元膜中 GM1 的不对称分布。基于向内和向外拉动的管状结构,我们开发了一种可以直接测量膜自发曲率的技术。通过囊泡电穿孔和荧光强度分析,我们能够定量测量 GM1 在膜中的不对称性,并随后估计分子在双层中产生的局部曲率。分子动力学模拟证实了实验确定的膜自发曲率与 GM1 不对称性的依赖性。GM1 在与受体蛋白的连接中起着至关重要的作用。我们关于 GM1 产生曲率的结果表明,这种神经节苷脂具有另一个重要作用,即塑造神经元膜。