Lipid Composition of the Cell Membrane Outer Leaflet Regulates Endocytosis of Nanomaterials through Alterations in Scavenger Receptor Activity.

Lipid Composition of the Cell Membrane Outer Leaflet Regulates Endocytosis of Nanomaterials through Alterations in Scavenger Receptor Activity.
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细胞膜外小叶的脂质组成通过改变清道夫受体活性来调节纳米材料的内吞作用。

DOI:
10.1021/acsnano.1c08344
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发表时间:
2022-02-22
期刊:
影响因子:
17.1
通讯作者:
Burdick, Monica M.
Burdick, Monica M.
中科院分区:
材料科学1区
文献类型:
--
作者:
Nazemidashtarjandi, Saeed;Sharma, Vishva M.;Puri, Vishwajeet;Farnoud, Amir M.;Burdick, Monica M.

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了解引导细胞摄取工程纳米材料(ENM)的原理在生物医学和职业健康研究中具有重要意义。虽然关于膜蛋白在ENM摄取中的作用的证据已经开始积累,但膜脂化学在调节ENM内吞作用中的作用在很大程度上仍未被探索。在这里,我们已经解决了这个问题,通过使用甲基-α-环糊精(M-α-CD)催化的脂交换方法直接改变活细胞中的质膜脂组成。我们在肺泡上皮细胞系中使用二氧化硅纳米颗粒进行的观察表明,质膜外叶的脂质成分通过影响ENM进入细胞内的非特异性扩散,改变膜流动性,以及改变参与活性内吞的清道夫受体(SR)的活性,在ENM内吞作用和ENM的细胞内命运中发挥重要作用。这些结果对于理解ENM在不同细胞亚群中的摄取具有重要意义,这取决于细胞膜的脂组成。
Understanding the principles that guide the uptake of engineered nanomaterials (ENMs) by cells is of interest in biomedical and occupational health research. While evidence has started to accumulate on the role of membrane proteins in ENM uptake, the role of membrane lipid chemistry in regulating ENM endocytosis has remained largely unexplored. Here, we have addressed this issue by altering the plasma membrane lipid composition directly in live cells using a methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange method. Our observations, in an alveolar epithelial cell line and using silica nanoparticles, reveal that the lipid composition of the plasma membrane outer leaflet plays a significant role in ENM endocytosis and the intracellular fate of ENMs, by affecting nonspecific ENM diffusion into the cell, changing membrane fluidity, and altering the activity of scavenger receptors (SRs) involved in active endocytosis. These results have implications for understanding ENM uptake in different subsets of cells, depending on cell membrane lipid composition.
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