Li Yuan, Chen Xiaolei, Lv Cheng, Cheng Yu
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Front Chem. 2023 Feb 28;11:1148699. doi: 10.3389/fchem.2023.1148699. eCollection 2023.
Transmembrane transport, mostly relying on biological channels, is crucial for the metabolic processes of live cells including sensing, signaling, cellular communicating and molecular transport. Artificial biomimetic channels offer excellent opportunities for studying the mechanisms of the metabolic processes of live cells and promote the applications of gene transfection, drug delivery, and regulations of cellular communications. DNA nanopores can be designed flexibly and operated easily while maintaining good biocompatibility, offering a good candidate for applications in basic research. However, because of the small size and good biocompatibility of DNA nanopores, it is still difficult to form stable channels on the plasma membrane of live cells by DNA nanopores. As a result, it significantly limits the applications of DNA nanopores . Thus, in this work, we have constructed ethane-phosphorothioate (PPT) groups modified DNA nanopores (E-DNA nanopores) to simulate biological channels for the transmembrane transport of small molecules. The E-DNA nanopores were found to be more hydrophobic and stable to anchor at the plasma membrane of live cells for a longer time window for subsequent transmembrane transport after the modification of ethane-PPT groups. The membrane-spanning E-DNA nanopores with a longer dwell time window could inspire the design of new DNA nanostructures and expand their biological applications including biosensing and sequencing, construction of artificial cells and regulation of transmembrane transport.
跨膜运输主要依赖生物通道,对于活细胞的代谢过程至关重要,包括传感、信号传导、细胞通讯和分子运输。人工仿生通道为研究活细胞代谢过程的机制提供了绝佳机会,并促进了基因转染、药物递送和细胞通讯调控等应用。DNA纳米孔可以灵活设计且操作简便,同时保持良好的生物相容性,是基础研究应用的理想候选者。然而,由于DNA纳米孔尺寸小且生物相容性好,仍然难以通过DNA纳米孔在活细胞质膜上形成稳定的通道。因此,这极大地限制了DNA纳米孔的应用。因此,在这项工作中,我们构建了乙烷硫代磷酸酯(PPT)基团修饰的DNA纳米孔(E-DNA纳米孔),以模拟用于小分子跨膜运输的生物通道。发现E-DNA纳米孔在修饰乙烷-PPT基团后更疏水且更稳定,能够在活细胞质膜上锚定更长时间窗口,用于后续的跨膜运输。具有更长驻留时间窗口的跨膜E-DNA纳米孔可以启发新型DNA纳米结构的设计,并扩展其生物应用,包括生物传感和测序、人工细胞构建以及跨膜运输调控。