Controlling Cargo Trafficking in Multicomponent Membranes
Controlling Cargo Trafficking in Multicomponent Membranes
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DOI：
10.1021/acs.nanolett.8b00786
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发表时间：
2018-09-01
期刊：
影响因子：
10.8
通讯作者：
Saric, Andela
中科院分区：
文献类型：
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作者：
Curk, Tine;Wirnsberger, Peter;Saric, Andela
生物膜通常含有大量以小浓度分散在主膜相中的不同组分，包括具有不同几何性质的蛋白质、糖和脂质。大多数这些组件不绑定货物。在这里，我们表明，这种“惰性”的成分可以是至关重要的跨膜运输的精确控制。使用统计力学模型和分子动力学模拟，我们证明了存在的惰性膜组件的小各向同性曲率显着影响货物内吞，即使这样的膜的总自发曲率保持不变。弯曲的脂质，如胆固醇，以及不对称包括蛋白质和拴系糖，因此，可以积极参与控制纳米级货物的膜运输。我们发现，即使是低水平表达的弯曲的惰性膜组件可以确定对货物大小的膜的选择性，并可用于选择性地靶向某些组合物的膜。我们的研究结果表明，一个强大的和一般的方法来控制货物运输，通过调整膜组成，而不需要改变受体的浓度或平均膜曲率。这项研究表明，细胞可以通过在任一膜小叶中掺入弯曲的惰性成分来为任何运输事件做好准备。
Biological membranes typically contain a large number of different components dispersed in small concentrations in the main membrane phase, including proteins, sugars, and lipids of varying geometrical properties. Most of these components do not bind the cargo. Here, we show that such "inert" components can be crucial for the precise control of cross-membrane trafficking. Using a statistical mechanics model and molecular dynamics simulations, we demonstrate that the presence of inert membrane components of small isotropic curvatures dramatically influences cargo endocytosis, even if the total spontaneous curvature of such a membrane remains unchanged. Curved lipids, such as cholesterol, as well as asymmetrically included proteins and tethered sugars can, therefore, actively participate in the control of the membrane trafficking of nanoscopic cargo. We find that even a low-level expression of curved inert membrane components can determine the membrane selectivity toward the cargo size and can be used to selectively target membranes of certain compositions. Our results suggest a robust and general method of controlling cargo trafficking by adjusting the membrane composition without needing to alter the concentration of receptors or the average membrane curvature. This study indicates that cells can prepare for any trafficking event by incorporating curved inert components in either of the membrane leaflets.