Controlling Membrane Translocation for Artificial Signal Transduction

点击翻译按钮获取中文摘要

The aim of the proposal is to develop chemical methods for controlling the motion of molecules backwards and forwards across lipid bilayer membranes. This molecular motion will be coupled to catalytic reactions inside vesicles, opening the way to a new class of chemical systems for sensing and signalling. Many of the unique properties and functions of complex biological systems arise from the compartmentalisation afforded by lipid bilayer membranes. These membranes form an important barrier between the cell's internal fluid and the external medium. However, extracellular molecules, such as hormones, nutrients and pathogens, can change the intracellular chemistry by signalling across the cell membrane via membrane-spanning proteins. Vesicles have the potential to store, amplify, transduce and communicate information in the same way as cells do, and this proposal aims to unlock this untapped capability in entirely synthetic systems, by coupling an external molecular recognition event with an internal catalytic process via 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 some specific and targeted way to an external signal such as a molecular binding event - which could be used in sophisticated sensing applications and targeted drug delivery. The compartmentalisation afforded by the bilayer membrane separates the inside and outside solutions and allows otherwise incompatible chemical processes and networks on the interior and exterior to co-exist independently. The development of synthetic constructs that facilitate transmembrane signalling is the first step towards realising compartmentalised-coupled chemistry, analogous to the complex phosphorylation cascades found in Nature. The ability to change the internal chemistry of a synthetic construct, such as a vesicle, in response to its external environment will offer new opportunities: coupling the external signal to an internal catalytic process (as biology does for amplification of weak molecular signals) has applications in sensing and diagnostics, or in 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.