Institute for Biological Interfaces (IBG-1), Karlsruhe Institute of Technology (KIT), 76344 Eggenstein-Leopoldshafen, Germany.
School of Engineering, University of Applied Sciences Upper Austria, 4600 Wels, Austria.
Nano Lett. 2024 Feb 7;24(5):1611-1619. doi: 10.1021/acs.nanolett.3c04272. Epub 2024 Jan 24.
The nanoscale arrangement of ligands can have a major effect on the activation of membrane receptor proteins and thus cellular communication mechanisms. Here we report on the technological development and use of tailored DNA origami-based molecular rulers to fabricate "Multiscale Origami Structures As Interface for Cells" (MOSAIC), to enable the systematic investigation of the effect of the nanoscale spacing of epidermal growth factor (EGF) ligands on the activation of the EGF receptor (EGFR). MOSAIC-based analyses revealed that EGF distances of about 30-40 nm led to the highest response in EGFR activation of adherent MCF7 and Hela cells. Our study emphasizes the significance of DNA-based platforms for the detailed investigation of the molecular mechanisms of cellular signaling cascades.
配体的纳米级排列会对膜受体蛋白的激活产生重大影响，从而影响细胞通讯机制。在这里，我们报告了基于定制 DNA 折纸的分子标尺的技术开发和应用，以制造“用于细胞的多尺度折纸结构”（MOSAIC），从而能够系统地研究表皮生长因子（EGF）配体的纳米级间距对 EGF 受体（EGFR）激活的影响。基于 MOSAIC 的分析表明，EGF 的距离约为 30-40nm 时，会导致贴壁 MCF7 和 Hela 细胞中 EGFR 激活的反应达到最高。我们的研究强调了基于 DNA 的平台在深入研究细胞信号级联分子机制方面的重要性。
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