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Plasma membrane functionalization using highly fusogenic immune activator liposomes

机译:使用高度融合的免疫激活剂脂质体的质膜功能化

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摘要

Cell surface functionalization and target molecule incorporation into living cell membranes without functional damage represent major biotechnological challenges. One possible way to achieve these goals is to induce cell membrane fusion with an artificial membrane containing molecules equipped with reactive groups or ligands. In this work we developed a carrier system to incorporate lipopolysaccharide (LPS), an immune cell activating molecule from Gram-negative bacteria, into mammalian membranes. LPS is not present in untreated mammalian cells which hence are not detectable by the immune system. Here, we demonstrate the successful incorporation of LPS into fusogenic liposomes (FLs) and subsequent incorporation into mammalian plasma membranes using these FLs. Additionally, the presence of LPS in cell membranes was probed by the addition of non-activated macrophages. A high concentration of LPS in the plasma membrane of immortalized fibroblasts activated the immune cells, which in turn started to eliminate LPS-exhibiting cells. Our method for cellular membrane functionalization is a promising tool for biomedical applications and could provide the basis for specific cell targeting approaches.
机译:细胞表面功能化和将靶分子掺入活细胞膜而没有功能损伤代表了主要的生物技术挑战。实现这些目标的一种可能方法是用包含带有反应性基团或配体的分子的人工膜诱导细胞膜融合。在这项工作中,我们开发了将脂多糖(LPS)(一种来自革兰氏阴性细菌的免疫细胞激活分子)掺入哺乳动物膜的载体系统。 LPS不存在于未处理的哺乳动物细胞中,因此无法被免疫系统检测到。在这里,我们证明了成功地将LPS并入融合脂质体(FLs)中,并随后使用这些FLs并入了哺乳动物的质膜中。另外,通过添加未活化的巨噬细胞来探测细胞膜中LPS的存在。永生化成纤维细胞质膜中高浓度的LPS激活了免疫细胞,从而开始消除表现LPS的细胞。我们的细胞膜功能化方法是生物医学应用中的有前途的工具,可以为特定细胞靶向方法提供基础。

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