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

合成组织包括有图案的二维或三维连通间隔集合，其中每个间隔类似于一个自然细胞，其内部为水，周围环绕着一层脂质双层膜。人工隔间可以包含各种天然和合成成分，以模拟自然的细胞过程。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。目前的一个挑战是制造具有功能成分的合成组织，这些成分可以被各种外部刺激远程控制，如化学信号、光或pH。特别是，可用于精确调节分子和离子在这些隔间之间流动的响应性分子组件缺乏。这些在人工隔间中的跨膜运输过程模仿了生物学中的那些过程，在生物学中，跨细胞膜的离子运输是由膜蛋白介导的，膜蛋白本身受到外部刺激的调节，如信号分子、膜电位和光。开发这些蛋白质的人工模拟物，称为合成离子转运体，是当前重要的研究领域，因为它们还提供了潜在的治疗应用，如囊性纤维化等离子通道故障引起的疾病，作为抗癌药物。在这个项目中，我们的目标是开发响应性离子转运体，其活性可以受到多种外部刺激(如光)的调节，并将这些系统应用于合成组织中。该项目的目标是开发反应灵敏的人工转运体，这种转运体可以很容易地利用合成化学来制备，以设计功能合成组织并控制间隔间的运输。该项目属于EPSRC的主题，即‘制造未来’和‘物理科学’，涉及“合成超分子化学”和“合成生物学”领域。通过开发可控制的组织状材料，有巨大的潜力为“多产和健康的国家成果”和“开发未来的治疗技术”的目标做出贡献。

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".