Outer membrane vesicles (OMVs) are spherical liposomes that are secreted by almost all forms of Gram-negative bacteria. The nanospheres contribute to bacterial pathogenesis by trafficking molecular cargo from bacterial membranes to target cells at the host-pathogen interface. We have simulated the interaction of OMVs with host cell membranes to understand why OMV uptake depends on the length of constituent lipopolysaccharide macromolecules. Using coarse-grained molecular dynamics simulations, we show that lipopolysaccharide lipid length affects OMV shape at the host-pathogen interface: OMVs with long (smooth-type) lipopolysaccharide lipids retain their spherical shape when they interact with host cell membranes, whereas OMVs with shorter (rough-type) lipopolysaccharide lipids distort and spread over the host membrane surface. In addition, we show that OMVs preferentially coordinate domain-favoring ganglioside lipids within host membranes to enhance curvature and affect the local lipid composition. We predict that these differences in shape preservation affect OMV internalization on long timescales: spherical nanoparticles tend to be completely enveloped by host membranes, whereas low sphericity nanoparticles tend to remain on the surface of cells.

中文翻译：

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感染或不感染：细菌外膜囊泡被宿主膜内化的分子决定因素。

外膜囊泡（OMV）是球形脂质体，几乎所有形式的革兰氏阴性细菌都会分泌这种脂质体。纳米球通过将分子货物从细菌膜运输到宿主-病原体界面的靶细胞来促进细菌发病。我们已经模拟了OMV与宿主细胞膜的相互作用，以了解为什么OMV的摄取取决于组成脂多糖大分子的长度。使用粗粒度的分子动力学模拟，我们显示脂多糖脂质长度会影响宿主-病原体界面处的OMV形状：长（光滑型）脂多糖脂质的OMV与宿主细胞膜相互作用时保持其球形，而较短的OMVs （粗糙型）脂多糖脂质在宿主膜表面变形并扩散。此外，我们表明，OMVs优先协调宿主膜内有利于域的神经节苷脂，以增强曲率并影响局部脂质组成。我们预测，形状保持的这些差异会在很长时间内影响OMV内在化：球形纳米颗粒倾向于被宿主膜完全包裹，而低球形纳米颗粒倾向于保留在细胞表面。