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Engineering a bacterial toxin alpha-hemolysin with Vitamin B12: Single Molceule Catalysis in the alpha-hemolysin nanoreactor

Final Report Summary - NANOREACTOR (Engineering a bacterial toxin alpha-hemolysin with Vitamin B12: Single Molceule Catalysis in the alpha-hemolysin nanoreactor)

The NANOREACTOR and the nanorobot

Nanotechnology is the manipulation of matter at the atomic or molecular scale allowing the direct control of matter at the atomic level. When assembled in very large numbers, nano-sised matter (1 - 100 nm) creates macroscopic objects with classical mechanical and physical properties. However, when employed in nano-scale clusters, they retain the special quantum mechanical and physical properties of the nano-world, enabling these nanoscopic assemblies to be applied on the frontier of several industries, including among many others the food industry, electronics, medicine and energy research.

One way to manufacture nano-sized matter is to build the matter by a bottom-up approach, such as self-assembly, self-recognition or any other physical attraction force (e.g. capillary effect) between molecules, which have been synthesised by classical synthetic chemical methods. Self-assembly is mostly directed by forces determined by the inherent properties of the molecules, limiting the ability to control such processes. As an alternative to self-assembly, the idea of 'controlled-assembly' has emerged. This way, any nanoscopic units could be carried to a desired location to react with or be tethered to each other. To achieve this, nano-machines or nano-robots are required. These molecular machines can carry out tasks including controlled delivery of replicating nano-units and controlling the location or rate of self-assembly processes.

In order to generate simple molecular machines, scientists have been by the biological cell machinery and looked at how cellular cargo is transported to target destinations by an army of motor proteins, such as kinesin or myosin. During their progression on the microtubule highways, the motor proteins convert the energy gained from hydrolysis of ATP into motion when carrying the cellular cargo to the desired locations.

In this project, the design of a nano-device with a synthetic molecular motor unit is described. The device consists of a biological track, which as well as a track scaffold, serves as the positional detection unit. The synthetic walker moves on the track by making reversible bonds between its reactive centre and the reactive points of the track. The design of the head of the synthetic walker allows the walker to be modified with different cargo molecules, resulting in a functional nano-machine with two parts. At the proof of concept stage, positional detection of the walker is achieved.

The outcomes of this project will pave the way to further discoveries of controlled machines for lab-on-chip type applications. These should enable for example the one-pot implementation of multi-pot synthetic procedures by the localisation of individual components, precise control of the rate and location of two reagents, and the directed assembly of nanoscopic systems.

Additionally, the discovery outlined in this project can lead to the development of controlled drug delivery systems which are compatible with biological membranes, highlighting the significance of this study in nano-medicine.

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