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DNA nanotweezers for stabilizing and dynamically lighting up a lipid raft on living cell membranes and the activation of T cells
Chemical Science ( IF 7.6 ) Pub Date : 2020/01/07 , DOI: 10.1039/c9sc06203c
Lele Sun 1, 2, 3, 4, 5 , Yingying Su 1, 2, 3, 4 , Jun-Gang Wang 1, 2, 3, 4 , Fei Xia 1, 2, 3, 4 , Ying Xu 3, 4, 6, 7, 8 , Di Li 1, 2, 3, 4
Affiliation  

Lipid rafts are generally considered as nanodomains on cell membranes and play important roles in signaling, viral infection, and membrane trafficking. However, the raft hypothesis is still debated with many inconsistencies because the nanoscale and transient heterogeneous raft structure creates difficulties in its location and functional analysis. In the present study, we report a DNA nanotweezer composed of a cholesterol-functionalized DNA duplex that stabilizes transient lipid rafts, which facilitate the further analysis of the raft component and its functions via other spectroscopy tools. The proposed DNA nanotweezer can induce clustering of raft-associated components (saturated lipids, membrane protein and possibly endogenous cholesterol), leading to the T cell proliferation through clustering of a T-cell antigen receptor (TCR). The flexibility of random sequence noncoding DNA provides versatile possibilities of manipulating lipid rafts and activating T cells, and thus opens new ways in a future T cell therapy.

中文翻译:

DNA纳米镊子可稳定并动态点亮活细胞膜上的脂质筏并激活T细胞

脂质筏通常被认为是细胞膜上的纳米域,并在信号传导,病毒感染和膜运输中起重要作用。然而,由于纳米尺度和瞬态的异质筏结构在其位置和功能分析上都遇到了困难,因此筏定假说仍存在许多矛盾之处。在本研究中,我们报道了一种由胆固醇官能化的DNA双链体组成的DNA纳米镊子,该双链体可稳定瞬时脂质筏,这有助于进一步分析筏组件及其功能其他光谱工具。拟议的DNA纳米镊子可以诱导筏相关成分(饱和脂质,膜蛋白和可能的内源性胆固醇)聚集,从而通过T细胞抗原受体(TCR)聚集导致T细胞增殖。随机序列非编码DNA的灵活性为操纵脂质筏和激活T细胞提供了多种可能性,从而为将来的T细胞疗法开辟了新途径。
更新日期:2020-02-13
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