Design and Synthesis of Ion Transporters for 3D Spatiotemporal Control in Synthetic Tissue

合成组织包括图案化的二维或三维连通区室集合，其中每个区室类似于具有由脂质双层膜包围的水性内部的天然细胞。人工隔室可以含有各种天然和合成组分，以模拟天然细胞过程。这些合成组织在组织工程、新型药物输送平台以及作为微型反应容器方面具有重要的潜在应用。目前的挑战是制造具有功能组件的合成组织，这些功能组件可以通过各种外部刺激（例如化学信号、光或pH）进行远程控制。特别是，缺乏可用于精确调节这些隔室之间的分子和离子流动的响应性分子组件。这些在人工隔室中跨膜的转运过程模拟了在生物学中发现的那些转运过程，其中跨细胞膜的离子转运由膜蛋白介导，膜蛋白本身由外部刺激如信号分子、膜电位和光调节。开发这些蛋白质的人工模拟物，称为合成离子转运蛋白，是当前重要的研究领域，因为它们也提供了潜在的治疗应用，用于治疗由离子通道故障引起的疾病，如囊性纤维化，作为抗癌剂。在本项目中，我们的目标是开发响应性离子转运蛋白，其活性可以通过多种外部刺激调节，如光，并将这些系统应用到合成组织中。本项目的目标是开发反应灵敏的人工转运蛋白，这些转运蛋白可以利用合成化学方法制备，以设计功能性合成组织并控制室间转运。本项目福尔斯属于EPSRC的“制造未来”和“物理科学”主题，并涉及“合成超分子化学”和“合成生物学”领域。通过开发可控的组织样材料，有很大的潜力，以促进“生产和健康的国家成果”和“开发未来的治疗技术”的目标。

Synthetic tissues comprise patterned two- or three-dimensional collections of communicating compartments, where each compartment resembles a natural cell with an aqueous interior surrounded by a lipid bilayer membrane. The artificial compartments may contain various natural and synthetic components in order to mimic natural cellular processes. These synthetic tissues have significant potential applications in tissue engineering, new drug delivery platforms, and as micro-sized reaction vessels. A current challenge is to fabricate synthetic tissues with functional components that can be remote-controlled by various external stimuli, such as chemical signals, light, or pH. In particular, responsive molecular components that can be used to precisely regulate the flow of molecules and ions between these compartments are lacking. These transport processes across membranes in artificial compartments mimic those found in biology, where ion transport across cell membranes is mediated by membrane proteins, which are themselves regulated by external stimuli such as by signalling molecules, membrane potential and light. Developing artificial mimics of these proteins, known as synthetic ion transporters, is an area of significant current research because they also offer potential therapeutic applications for diseases that arise from malfunctioning ion channels, such as cystic fibrosis, as anticancer agents.In this project, we aim to develop responsive ion transporters, whose activity can be regulated by multiple external stimuli such as light, and apply these systems within synthetic tissues. The aim is to develop responsive, artificial transporters that can be prepared readily using synthetic chemistry, to engineer functional synthetic tissues and control inter-compartment transport.This project falls within the EPSRC themes of 'manufacturing the future' and 'physical sciences', and relates to the area of "synthetic supramolecular chemistry" and "synthetic biology". By developing controllable tissue-like materials, there is significant potential to contribute to the goals of "Productive and Healthy Nation Outcomes" and "develop future therapeutic technologies".