Controlling membrane translocation for artificial signal transduction
Lead Research Organisation:
University of Sheffield
Department Name: Chemistry
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Organisations
People |
ORCID iD |
| Nicholas Williams (Principal Investigator) |
Publications
Ding Y
(2019)
A Synthetic Vesicle-to-Vesicle Communication System.
in Journal of the American Chemical Society
Kocsis I
(2021)
Transmembrane signal transduction by cofactor transport.
in Chemical science
| Description | We have developed synthetic vesicles (simple mimics of cells that have an internal space separated from their surroundings by a bilayer membrane) that can respond to a range of chemical signals in their environment by giving a different internal response. The chemical signals have been based on pH, metal ion binding, redox switching and protein-ligand interactions. We have developed ways of making the molecules that are central to the system in a more general way, and identified ways in which the membranes we use affect the response of the system. Two different catalytic systems have been developed that amplify the response to these chemical signals inside the vesicles. One system is based on simple carboxylic ester hydrolysis, and the other was based on phosphate diester hydrolysis. This means that a wide range of potential substrates can be used on the inside of the vesicles to produce an equally wide range of products generated on the inside of the vesicles to give an observable signal or a chemical response. The internal signal can be coupled to a series of reactions that make the vesicle membrane permeable, thereby releasing the material it carries to the external solution. The ability to change the internal chemistry of a vesicle in response to its external environment has applications in sensing and diagnostics, or in the catalytic activation of a pro-drug for controlled-release applications, and provides a platform for the construction of biocompatible interfaces for communication with cellular systems. |
| Exploitation Route | We have developed novel responsive vesicle assemblies that create internal signals in response to changes in their environment. These signals can be physical, so that the reaction to different environmental changes can be observed through spectroscopy, or chemical, where the products can leave the vesicle and influence the environment. These systems work in water and have the potential to interface with biological systems, particularly cell surfaces, which they resemble. Applications can be envisaged in the development of drug delivery systems that release active compounds at a specific site in response to a specific signal. An attractive feature of the supramolecular design is that the output signal that is generated can be amplified by the catalytic cascade it is designed around which is similar to the processes used in biological signalling. This amplification provides the opportunity for the development of new types of sensor with extremely high sensitivity. There is no doubt that nanotechnology will have a huge impact across the industrialised societies in the coming decades, and the development of complex multiple component molecular machines such as the one described in this proposal will underpin the development of these new technologies. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | The impact of this work is recorded against grant ref EP/R005397/1 |
| First Year Of Impact | 2022 |