Nature ( IF 50.5 ) Pub Date : 2024-12-04 , DOI: 10.1038/s41586-024-08203-4 Hao Gong, Yuriko Sakaguchi, Tsutomu Suzuki, Miho Yanagisawa, Takuzo Aida
Although separation is entropically unfavourable, it is often essential for our life1,2. The separation of very similar macromolecules such as deoxyribonucleic acids (DNAs) and their single nucleotide variants is difficult but holds great advantage for the progress of life science3. Here we report that a particular liquid–liquid phase separation (LLPS) at a solid–liquid interface led to the partitioning of DNAs with nearly identical structures. We found this intriguing phenomenon when we did drop-casting onto a glass plate an aqueous ammonium sulfate dispersion of phase-separated droplets comprising a homogeneous mixture of poly(ethylene glycol) (PEG) samples with different termini. Even when the molecular weights of their PEG parts were identical to each other, terminally different PEGs spread competitively at the solid–liquid interface and partitioned into micrometre-scale concentric circles. We found that this competitive spreading was induced by an ammonium sulfate layer spontaneously formed on the glass surface. We successfully extended the above mechanism to partitioning a mixture of nearly identical DNAs into concentric circles followed by their selective extraction using the salting-in effect. We could isolate a human cancer-causing single nucleotide variant in 97% purity from its 1:1 mixture with the original DNA.
中文翻译:
几乎相同的大分子自发地分配成同心圆
尽管分离在熵上是不利的,但它通常对我们的生活至关重要1,2。分离非常相似的大分子,如脱氧核糖核酸 (DNA) 及其单核苷酸变体,虽然困难重重,但对生命科学的进步具有很大的优势3。在这里,我们报道了固-液界面上的特定液-液相分离 (LLPS) 导致具有几乎相同结构的 DNA 分配。当我们将相分离液滴的硫酸铵水分散体滴注到玻璃板上时,我们发现了这种有趣的现象,该液滴由具有不同末端的聚乙二醇 (PEG) 样品的均相混合物组成。即使它们的 PEG 部分的分子量彼此相同,最终不同的 PEG 也会在固液界面处竞争性地传播,并被分成微米级的同心圆。我们发现这种竞争性扩散是由玻璃表面自发形成的硫酸铵层诱导的。我们成功地将上述机制扩展到将几乎相同的 DNA 混合物分成同心圆,然后使用盐渍效应对其进行选择性提取。我们可以从与原始 DNA 的 1:1 混合物中分离出纯度为 97% 的人类致癌单核苷酸变体。