Researchers have developed a new technique to analyze cell membrane proteins in situ which could revolutionize the way in which we study diseases, such as cancer, metabolic and heart diseases.

Researchers have developed a new technique to analyze cell membrane proteins in situ which could revolutionize the way in which we study diseases, such as cancer, metabolic and heart diseases.

The discovery was made as part of an international research collaboration, led by Oxford University, alongside peers including Imperial College London. The technique could dramatically affect our understanding of both how cell membrane complexes work, and in the process, our approach to healthcare research.

Membranes protect all of our cells and the organelles inside them, including the mitochondria – the powerhouse of the cell. These membranes are studded with biological machinery made of proteins that enable molecular charge to pass in and out.

Mass Spectroscopy

This research, published in  Science, will enable the development of mass spectrometry (a tool used to analyze the make-up of matter) in biology to be taken to a new level, enabling new discoveries that would not have been possible before.

Studying these membrane-embedded machines in their native state is crucial to understanding mechanisms of disease and providing new goals for treatments. However, current methods for studying them involve removing them from the membrane, which can alter their structure and functional properties.

Lead researcher Professor Dame Carol Robinson, Professor of Physical Chemistry at Oxford's Department of Chemistry, said: 'For decades, scientists have had to extract these proteins from their membranes for their studies. But imagine what you might discover if you could get proteins straight from the membrane into a mass spectrometer?

I was not sure this would ever work; I thought the membrane environment would be just too complicated and we would not be able to understand the results. I am delighted that it is because it has given us a whole new view of an important class of drug targets. '

Ultrasonic frequencies 

The technique involves vibrating the sample at ultrasonic frequencies so that the cell begins to fall apart. Electrical currents then applied to an electric field to eject the protein out of the membrane and directly into a mass spectrometer – an instrument that can detect a chemical's signature, based on its mass.

Not only did the membrane protein machines survive the ejection; the analysis also revealed how they communicate with each other, they are guided to their final location and transport their molecular charge into the cell.

Professor Steve Matthews, from the Department of Life Sciences at Imperial, said: 'With the development of this method, the application of mass spectrometry in biology will be taken to a new level, using it to make discoveries that would not have been possible before.'

Mitochondrial therapeutics 

Dr Sarah Rouse, also from the Department of Life Sciences at Imperial, said: 'A longstanding question on the structure of one membrane machine from mitochondria has now been solved using this technique. Mitochondria are particularly interesting because there are several diseases that target them specifically, that we are now able to design new therapies for.

Of the study's potential impact Professor Dame Robinson added: "The results are particularly exciting for mitochondrial membranes – we managed to catch a translocator in action – passing metabolites, because mitochondrial therapeutics target a wide range of debilitating diseases, we now have a new way of assessing their effects. '