Bilateral NSF/BIO-BBSRC: Synthetic DNA Nanopores for Selective Transmembrane Transport

小分子的跨生物膜运输对细胞来说是必不可少的；它能够清除细胞中的废物，补充营养物质，并分泌信使分子。蛋白质孔和通道通常对特定的货物具有选择性，并具有定义的宽度和表面电荷，从而促进了能量无关的运输。所有已知的跨膜孔都是由蛋白质组成的。在合成生物学中，需要设计一种新的毛孔，适合移动一种货物。在这个合作项目中，来自美国(亚利桑那州立大学)和英国(伦敦大学学院)的研究人员结合了膜纳米孔研究和DNA纳米技术的专业知识，产生了在性质上类似于蛋白质孔但由DNA组成的新型膜孔。该项目利用最近在简单膜跨DNA纳米孔方面的突破，建立了大小、电荷性质和活性可调的结构和功能先进的孔。DNA纳米孔的设计和构造将能够实现对孔径、电荷选择性和刺激控制活动的可编程调节。具有可预测结构的DNA纳米孔将被定制用于应用，包括开发用于光触发释放细胞生物学研究中有用的蛋白质的膜室，以及用于局部激活抗癌前体药物的酶促膜纳米反应器。

Transport of small molecules across biological membranes is essential for cells; it enables removal of waste from cells, replenishing of nutrients, and secretion of messenger molecules. Energy-independent transport is facilitated by protein pores and channels that often are selective for a particular cargo, and have defined width and surface charge. All known transmembrane pores are made of protein. In synthetic biology, there is a need to design new kinds of pores, suitable for moving one kind of cargo. In this collaborative project, investigators from the US (Arizona State University) and the UK (University College London) combine expertise from membrane nanopore research and DNA nanotechnology to generate novel versions of membrane pores that are similar in properties to protein pores but are made of DNA.The project exploits the recent breakthrough on simple membrane-spanning DNA nanopores and build structurally and functionally advanced pores of tunable size, charge properties, and activity. DNA nanopores will be designed and constructed to enable the programmable tuning of pore diameter, charge selectivity, and stimulus-controlled activities. The DNA nanopores of predictable structures will be tailored for applications including the development of membrane compartments for light-triggered release of proteins useful in cell biological research, and enzymatic membrane nanoreactors for the localized activation of anti-cancer prodrugs.