日本东京大学Aida Takuzo团队报道了几乎相同的大分子自发地分裂成同心圆。相关研究成果于2024年12月4日发表于国际一流学术期刊《自然》。

虽然分离在熵方面是不利的，但它对我们的生活往往至关重要。脱氧核糖核酸（DNAs）及其单核苷酸变体等非常相似的大分子的分离是困难的，但对生命科学的进步具有巨大的优势。

该文中，研究认为固液界面上的一种特殊的液-液相分离（LLPS），导致了具有几乎相同结构的DNAs的分配。当研究人员在玻璃板上滴注相分离液滴的硫酸铵水分散体时，发现了这一有趣的现象，该分散体由具有不同末端的聚乙二醇（PEG）样品的均匀混合物组成。即使它们的PEG部分的分子量彼此相同，末端不同的PEGs也会在固液界面上竞争性地扩散，并被分成微米级的同心圆。

研究发现，这种竞争性扩散是由玻璃表面自发形成的硫酸铵层引起的。研究人员成功地将上述机制扩展到，将几乎相同的DNAs混合物分成同心圆，然后使用盐析效果进行选择性提取。研究人员可以从与原始DNA 1:1的混合物中，分离出纯度为97%的人类致癌单核苷酸变体。

附：英文原文

Title: Near-identical macromolecules spontaneously partition into concentric circles

Author: Gong, Hao, Sakaguchi, Yuriko, Suzuki, Tsutomu, Yanagisawa, Miho, Aida, Takuzo

Issue&Volume: 2024-12-04

Abstract: 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.

DOI: 10.1038/s41586-024-08203-4

Source: https://www.nature.com/articles/s41586-024-08203-4