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.

中文翻译：

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控制多组分膜中的货物运输

生物膜通常包含大量不同成分，这些成分以很小的浓度分散在主膜相中，包括具有不同几何特性的蛋白质，糖和脂质。这些组件中的大多数不束缚货物。在这里，我们表明，这种“惰性”成分对于精确控制跨膜运输至关重要。使用统计力学模型和分子动力学模拟，我们证明了各向同性曲率小的惰性膜成分的存在会极大地影响货物的内吞作用，即使这种膜的总自发曲率保持不变。因此，弯曲的脂质（例如胆固醇）以及不对称包含的蛋白质和束缚糖可以积极参与纳米货物膜运输的控制。我们发现，即使是弯曲的惰性膜成分的低水平表达也可以确定膜对货物尺寸的选择性，并且可以用于选择性地靶向某些组成的膜。我们的结果表明，通过调节膜的组成而不需要改变受体的浓度或平均膜曲率，就可以控制货物运输的鲁棒性和通用性。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准备。我们的结果表明，通过调节膜的组成而不需要改变受体的浓度或平均膜曲率，就可以控制货物运输的鲁棒性和通用性。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准备。我们的结果表明，通过调节膜的组成而不需要改变受体的浓度或平均膜曲率，就可以控制货物运输的鲁棒性和通用性。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。