Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen 76344, Germany.
Zoological Institute, Karlsruhe Institute of Technology, Karlsruhe 76131, Germany.
Nano Lett. 2023 Sep 13;23(17):7815-7824. doi: 10.1021/acs.nanolett.3c01301. Epub 2023 Aug 16.
Stem cells exhibit prominent clusters controlling the transcription of genes into RNA. These clusters form by a phase-separation mechanism, and their size and shape are controlled via an amphiphilic effect of transcribed genes. Here, we construct amphiphile-nanomotifs purely from DNA, and we achieve similar size and shape control for phase-separated droplets formed from fully synthetic, self-interacting DNA-nanomotifs. Increasing amphiphile concentrations induce rounding of droplets, prevent droplet fusion, and, at high concentrations, cause full dispersal of droplets. Super-resolution microscopy data obtained from zebrafish embryo stem cells reveal a comparable transition for transcriptional clusters with increasing transcription levels. Brownian dynamics and lattice simulations further confirm that the addition of amphiphilic particles is sufficient to explain the observed changes in shape and size. Our work reproduces key aspects of transcriptional cluster formation in biological cells using relatively simple DNA sequence-programmable nanostructures, opening novel ways to control the mesoscopic organization of synthetic nanomaterials.
干细胞表现出突出的簇，控制基因转录成 RNA。这些簇通过相分离机制形成，其大小和形状通过转录基因的两亲性效应控制。在这里，我们完全从 DNA 构建了两亲性纳米结构，并对完全由自相互作用的 DNA 纳米结构形成的相分离液滴实现了类似的大小和形状控制。增加两亲性浓度会导致液滴变圆，阻止液滴融合，并且在高浓度下会导致液滴完全分散。从小鼠胚胎干细胞中获得的超分辨率显微镜数据显示，随着转录水平的增加，转录簇也会发生类似的转变。布朗动力学和晶格模拟进一步证实，添加两亲性颗粒足以解释所观察到的形状和大小变化。我们的工作使用相对简单的 DNA 序列可编程纳米结构再现了生物细胞中转录簇形成的关键方面，为控制合成纳米材料的介观组织开辟了新途径。
