Extracellular vesicles (EVs) represent a potent intercellular communication system. Within a lipid bilayer such small vesicles transport biomolecules between cells and throughout the body, strongly influencing the fate of recipient cells. Due to their specific biological functions they have been proposed as biomarkers for various diseases and as optimal candidates for therapeutic applications. Despite of their extreme biological relevance, the small size (30 to a few hundred nanometers in diameter) of EVs still poses a great challenge for their isolation, quantification and biophysical/biochemical characterization, therefore the complex network of EVs and cells as well as their interaction remains to be further revealed. Here we propose a multiscale platform based on Atomic Force Microscopy, Small Angle X-ray Scattering, Small Angle Neutron Scattering and Neutron Reflectometry to reveal structure-function correlations of purified EVs through the analysis of their interaction with model membrane systems, in form of both supported lipid bilayers and suspended unilamellar vesicles of variably complex composition. The analysis reveals a strong interaction of EVs with the model membranes and preferentially with liquid ordered raft-like lipid domains, and opens the way to understand uptake mechanisms in different vesicle to cell membrane relative compositions.

中文翻译：

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血浆细胞膜与模型血浆膜融合机制的结构研究

细胞外囊泡（EVs）代表有效的细胞间通讯系统。在脂质双层中，这样的小囊泡在细胞之间以及整个身体中运输生物分子，强烈影响受体细胞的命运。由于其特定的生物学功能，它们已被提议作为各种疾病的生物标志物和治疗应用的最佳候选者。尽管它们具有极端的生物学意义，但小体积的电动汽车（直径为30至几百纳米）仍然对其分离，定量和生物物理/生化特征构成了巨大挑战，因此，电动汽车，细胞以及它们的复杂网络互动仍有待进一步揭示。在这里，我们提出一个基于原子力显微镜，小角度X射线散射，小角度中子散射和中子反射法通过分析其与模型膜系统的相互作用，揭示了纯化的电动汽车的结构-功能相关性，形式为支持的脂质双层和具有可变复杂组成的悬浮单层囊泡。该分析揭示了电动汽车与模型膜之间的强相互作用，并优先与液体有序筏状脂质结构域相互作用，并为理解不同囊泡对细胞膜相对组成的摄取机制开辟了道路。