Nanoparticles, on exposure to the biological milieu, tend to interact with macromolecules to form a biomolecular corona. The biomolecular corona confers a unique biological identity to nanoparticles, and its protein composition plays a deterministic role in the biological fate of nanoparticles. The physiological behavior of proteins stems from their physicochemical properties, including surface charge, hydrophobicity, and structural stability. However, there is insufficient understanding about the role of physicochemical properties of proteins in biomolecular corona formation. We hypothesized that the physicochemical properties of proteins would influence their interaction with nanoparticles and have a deterministic effect on nanoparticle-cell interactions. To test our hypothesis, we used model proteins from different structural classes to understand the effect of secondary structure elements of proteins on the nanoparticle-protein interface. Further, we modified the surface of proteins to study the role of protein surface characteristics in governing the nanoparticle-protein interface. For this study, we used mesoporous silica nanoparticles as a model nanoparticle system. We observed that the surface charge of proteins governs the nature of the primary interaction and the extent of subsequent secondary interactions causing structural rearrangements of the protein. We also observed that the secondary structural contents of proteins significantly affected both the extent of secondary interactions at the nanoparticle-protein interface and the dispersion state of the nanoparticle-protein complex. Further, we studied the interactions of different protein-coated nanoparticles with different cells (fibroblast, carcinoma, and macrophage). We observed that different cells internalized the nanoparticle-protein complex as a function of secondary structural components of the protein. The type of model protein had a significant effect on their internalization by macrophages. Overall, we observed that the physicochemical characteristics of proteins had a significant role in modulating the nanoparticle-bio-interface at the level of both biomolecular corona formation and nanoparticle internalization by cells.

中文翻译：

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蛋白质的理化性质在调节纳米粒子-生物界面中的作用。

纳米粒子在暴露于生物环境后，往往会与大分子相互作用以形成生物分子电晕。生物分子电晕赋予纳米颗粒独特的生物学特性，其蛋白质组成在纳米颗粒的生物学命运中起决定性作用。蛋白质的生理行为源自其理化特性，包括表面电荷，疏水性和结构稳定性。但是，对蛋白质的物理化学性质在生物分子电晕形成中的作用还没有足够的了解。我们假设蛋白质的物理化学性质将影响其与纳米粒子的相互作用，并对纳米粒子与细胞的相互作用具有确定性的影响。为了检验我们的假设，我们使用来自不同结构类别的模型蛋白质来了解蛋白质二级结构元素对纳米粒子-蛋白质界面的影响。此外，我们修饰了蛋白质的表面，以研究蛋白质表面特征在控制纳米粒子-蛋白质界面中的作用。在本研究中，我们使用介孔二氧化硅纳米颗粒作为模型纳米颗粒系统。我们观察到蛋白质的表面电荷控制着主要相互作用的性质和随后引起蛋白质结构重排的次级相互作用的程度。我们还观察到蛋白质的二级结构含量显着影响了纳米粒子-蛋白质界面处的二级相互作用程度和纳米粒子-蛋白质复合物的分散状态。进一步，我们研究了不同蛋白包被的纳米颗粒与不同细胞（成纤维细胞，癌和巨噬细胞）的相互作用。我们观察到，不同的细胞将纳米粒子-蛋白质复合物内化为蛋白质的二级结构成分的函数。模型蛋白的类型对其通过巨噬细胞的内在化具有显着影响。总体而言，我们观察到蛋白质的理化特性在调节生物分子电晕形成和细胞内在的纳米颗粒内在化方面对调节纳米颗粒-生物界面具有重要作用。模型蛋白的类型对其通过巨噬细胞的内在化具有显着影响。总体而言，我们观察到蛋白质的理化特性在调节生物分子电晕形成和细胞内在的纳米颗粒内在化方面对调节纳米颗粒-生物界面具有重要作用。模型蛋白的类型对其通过巨噬细胞的内在化具有显着影响。总体而言，我们观察到蛋白质的理化特性在调节生物分子电晕形成和细胞内在的纳米颗粒内在化方面对调节纳米颗粒-生物界面具有重要作用。