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的交流室集合，其中每个室类似于一个天然细胞，内部是水，周围是脂质双层膜。人造隔室可以包含各种天然和合成成分，以模拟自然细胞过程。这些合成组织在组织工程、新型药物输送平台和微型反应血管等方面具有重要的潜在应用价值。目前的挑战是制造具有功能成分的合成组织，这些功能成分可以被各种外部刺激（如化学信号、光或ph）远程控制。特别是，可用于精确调节这些隔间之间分子和离子流动的响应性分子成分是缺乏的。这些在人工隔室中跨膜的运输过程模拟了生物学中发现的过程，其中离子跨细胞膜的运输是由膜蛋白介导的，膜蛋白本身受外部刺激（如信号分子、膜电位和光）的调节。开发这些蛋白质的人工模拟物，被称为合成离子转运体，是当前重要的研究领域，因为它们也为由离子通道故障引起的疾病提供了潜在的治疗应用，如囊性纤维化，作为抗癌剂。在这个项目中，我们的目标是开发响应性离子转运体，其活性可以通过多种外部刺激如光来调节，并将这些系统应用于合成组织中。目的是开发反应灵敏的人工转运体，可以利用合成化学制备，设计功能性合成组织并控制隔室间运输。该项目属于EPSRC“制造未来”和“物理科学”的主题，涉及“合成超分子化学”和“合成生物学”领域。通过开发可控制的类组织材料，有很大的潜力有助于实现“富有成效和健康的国家成果”和“发展未来的治疗技术”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".