Laser fluorescence technology highlights cell surface protein
receptors in real time
9 September 2008
Researchers at The University of Nottingham have developed laser
fluorescence technology that enables observation of protein activity on
living cell surfaces for the first time.
The cutting-edge technology has helped to attract a £1.3 million
grant from the UK Medical Research Council for a five-year project that
will offer new insights into chemical activity taking place within
single cells. It could contribute to the design of new drugs to treat
human inflammatory diseases such as asthma and arthritis with fewer side
The team, involving Professor Steve Hill and Dr Steve Briddon from
the University’s School of Biomedical Science and Dr Barrie Kellam from
the School of Pharmacy, is concentrating on a type of specialised
docking site (receptor) on the surface of a cell that recognises and
responds to a natural chemical within the body called adenosine.
These A3-adenosine receptors work within the body by binding with
proteins to cause a response within cells and are found in very tiny and
highly specialised area of a cell membrane called microdomains.
Microdomains contain a collection of different molecules that are
involved in telling the cell how to respond to drugs or hormones.
It is believed that these receptors play an important role in
inflammation within the body and knowing more about how they operate
could inform the future development of anti-inflammatory drugs that
target just those receptors in the relevant microdomain of the cell,
without influencing the same receptors in other areas of the cell.
However, scientists have never before been able to look in detail at
their activity within these tiny microscopic regions of a living cell.
The Nottingham researchers have solved this problem by creating novel
drug molecules which have fluorescent labels attached. Using a cutting
edge laser technology called fluorescence correlation spectroscopy, the
fluorescent drug molecules can be detected as they glow under the laser
beam of a highly sensitive microscope. This allows their binding to the
receptor to be followed for the first time in real time at the single
A fluorescent drug (in red) binding to an
adenosine receptor on the surface of living cells.
Leading the project, Professor Steve Hill in the School of Biomedical
Sciences said: “These microdomains are so tiny you could fit five
million of them on a full stop. There are 10,000 receptors on each cell,
and we are able to follow how single drug molecules bind to individual
receptors in these specialised microdomains.
“What makes this single molecule laser technique unique is that we
are looking at them in real time on a living cell. Other techniques that
investigate how drugs bind to their receptors require many millions of
cells to get a big enough signal and this normally involves destroying
the cells in the process”
The researchers will be using donated blood as a source of
A3-receptors in specialised human blood cells (neutrophils) that have
important roles during inflammation.
Different types of adenosine receptors are found all over the body
and can exist in different areas of the cell membrane and have different
properties. Scientists hope that eventually the new technology could
also be used to unlock the secrets of the role they play in a whole host
of human diseases.
The fluorescent molecules developed as part of the research project
will also be useful in drug screening programmes and The University of
Nottingham will be making these fluorescent drugs available to the wider
scientific community through its links with its spin-out company
CellAura Technologies Ltd.