CATSIG: Synthesis and study of catalytic signalling systems to create vesicles that mimic cell sensing and signalling

复杂生物系统的一个关键特征是由脂类双层膜提供的区隔。这将内部和外部溶液分开，并允许内部和外部不兼容的化学过程和网络独立共存。然而，至关重要的是，细胞外的分子，如激素、营养物质和病原体，可以改变细胞内的化学物质--这是通过跨细胞膜的信号传递实现的，通常是通过跨膜蛋白质，引发一连串的反应，这些反应既放大又传递原始信号，以便细胞能够做出适当的反应。囊泡是细胞的简化类似物，具有以同样的方式存储、放大、转导和交流信息的潜力，该提议旨在用完全合成的系统在功能上模拟细胞的反应。其目的是利用一种新的跨膜信号转导途径，将外部分子识别事件与内部催化过程相结合。囊泡已经用于药物输送应用，但响应性囊泡具有巨大的潜力--那些能够以特定和靶向的方式对外部信号做出反应的囊泡，例如分子结合事件--可以用于靶向药物输送，例如催化激活前体药物以用于控制释放应用。此外，能够有效传递化学信息的多价囊泡将为构建生物兼容接口提供一个平台，用于与复杂的传感应用和诊断的细胞系统进行通信。

A critical feature of complex biological systems is the compartmentalisation provided by lipid bilayer membranes. This separates the inside and outside solutions and allows otherwise incompatible chemical processes and networks on the interior and exterior to co- exist independently. However, it is critical that extracellular molecules, such as hormones, nutrients and pathogens, can change the intracellular chemistry - and this is achieved by signalling across the cell membrane, usually via membrane-spanning proteins, which trigger a cascade of reactions which both amplify and transduce the original signal so that the cell can respond appropriately. Vesicles are simplified analogues of cells, and have the potential to store, amplify, transduce and communicate information in the same way, and this proposal aims to functionally mimic the cellular response with entirely synthetic systems. The aim is to couple an external molecular recognition event with an internal catalytic process using a novel transmembrane signal transduction pathway. Vesicles are already used in drug-delivery applications, but there is huge potential for responsive vesicles - those that can react in a specific and targeted way to an external signal such as a molecular binding event - which could be used in targeted drug delivery, such as the catalytic activation of a pro-drug for controlled-release applications. Furthermore, multivalent vesicles that are capable of efficient transduction of chemical information will provide a platform for the construction of biocompatible interfaces for communication with cellular systems for sophisticated sensing applications and diagnostics.