X-rays shed new light on muscle regulation
Posted on 12/04/2011
Where the experiment took place
An international group of scientists has used a powerful new X-ray technique to observe for the first time at the molecular scale how muscle proteins change form and structure inside a contracting muscle cell.
The study, led by scientists from King’s College London, Università di Firenze (Italy), and the European Synchrotron Radiation Facility (ESRF) in Grenoble (France), is published in the latest issue of the Proceedings of the National Academy of Sciences (PNAS).
A muscle cell contains two sets of filaments composed of the proteins actin and myosin, respectively. Muscles contract as a result of the relative sliding of these filaments. When the brain sends a nerve signal to activate a muscle, the electrical signal is transmitted to the muscle cell. This sets off a chain of events inside the muscle cell that eventually leads to changes in the structure of the myosin and actin filaments.
But what exactly happens during this process at the molecular level? ‘As we need muscles for locomotion, breathing and body posture, and for the contraction of the heart, understanding of these mechanisms has broad significance in biology and medicine’, says Professor Malcolm Irving from the Randall Division of Cell and Molecular Biophysics at King’s.
Studying a single intact and contracting muscle cell at the molecular scale in milliseconds became possible thanks to a new technique called X-ray interferometry based on low angle diffraction. This requires the extremely intense and narrow beam of X-rays provided by the ESRF.
The results of the experiment reveal the conformation of the head domains of myosin—the molecular motors that drive filament sliding—in resting muscle, and show that the movements of the myosin motors following muscle activation are much slower than the structural changes in the actin filaments. The different timings of the structural changes reveal the signalling pathway between the actin and myosin filaments in muscle, shedding new light on the mechanism of muscle regulation.
‘We were observing quite rapid biological processes, in the order of milliseconds, along with minuscule structural changes, typically 10 nm or less. A human hair is ten-thousand times thicker. To integrate the mechanical and X-ray diffraction methods that are required to resolve the combination of these extremes is a real experimental challenge’, explains Vincenzo Lombardi from the Unversity of Florence.
A longer-term clinical impact of this study may be in the area of heart disease, in which these fundamental signalling mechanisms are not working optimally in the heart muscle. Existing drugs to treat heart failure by modulating this signalling pathway are far from ideal. ‘To develop better drugs for heart failure, it’s likely that a better understanding of the molecular mechanisms of muscle regulation is needed, and that may be the long-term contribution of our experiments,’ concludes Professor Irving.
Notes to editors
* Image courtesy of P.Ginter, ESRF
King's College London
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