To begin bridging this gap in our understanding, Professors Brady and Virji teamed up with Dr Massimo Antognozzi from the University's School of Physics, whose group have been developing a novel form of atomic force microscope, termed the lateral molecular force microscope (LMFM).
Together, they have evolved the design of the LMFM microscope to optimise its ability to measure biological phenomena such as changes in UspA1 directly at the Moraxella cell surface. The LMFM differs from more conventional atomic force microscopes in tapping samples (in this case, individual cells) against an extremely fine lever, equivalent to the stylus of a record player, rather than moving the lever as is usually the case. Fabrication of extremely thin but stiff cantilevers together with exceptionally fine motor movements and a specialised visualisation system have all been combined in the device to tremendous effect. The sensitivity achieved has been further enhanced by its location within the extremely low vibration environment provided within the University's innovative Nanoscience and Quantum Information building. The result has been a machine that can measure exquisitely fine molecular changes and forces in individual molecules directly on a living cell surface.
In the Moraxella study, this development has enabled the research team to correlate intricate, atomic level detail of UspA1 obtained by X-ray crystallography of isolated fragments of the protein with delicate and previously unobservable physical changes of the bacterial cell as it binds to and infects its target human cells.
Professor Brady said: "The findings have triggered the development of a novel technology that promises to open up a new approach for studying molecular medicine. This breakthrough will undoubtedly prove equally useful for the study of many other biological processes directly within their cellular environment, something
|Contact: Caroline Clancy|
University of Bristol