The image helps researchers understand how heart muscles operate in disease.
An international team led by the Max Planck Institute in Dortmund, Germany, and King’s College London, have shot the first-ever high-resolution 3D image of the thick filament of a mammalian heart muscle, shedding light on heart and muscle health.
Scientists will now be able to develop innovative pharmacological approaches and treatments to target heart and muscle disorders by understanding their functions.
When the heart contracts, or beats, thick and thin protein filaments interact within the sarcomere, the basis of both skeletal and heart muscle cells.
Severe health consequences can occur when thick filament proteins experience alterations, which can lead to conditions such as hypertrophic cardiomyopathy, a condition which affects the left ventricle of the heart.
Additionally, alterations can lead to various other heart and muscle diseases.
The Max Planck Institute developed an electron cryo-tomography workflow, a 3D nanometre-resolution imaging technique of the inner workings of cells, to specifically tailor the muscle samples being investigated.
This process involved flash-freezing mammalian heart muscle samples, provided by the team at King’s College London, at temperatures as low as -175°C and applying a focus ion beam (FIB milling) to thin out samples to an ideal thickness for the transmission electron microscope.
The transmission electron microscope obtains multiple images as the sample is tilted along an axis, which leads to the reconstruction of a three-dimensional, high-resolution picture.
The King’s College London team then validated the molecular interpretation of the 3D images produced using super-resolution fluorescence microscopy to reveal the position of molecules accurately.
The high-resolution image offers insight into the molecular organisation and arrangement of the components within the thick filament, which provides a crucial framework for understanding how muscles operate in both health and disease.
Professor Mathias Gautel, British Heart Foundation chair, molecular cardiology, King’s College London, said: “This study has revealed the unexpected complexity of the shapes of the molecules building the thick filaments that will be important to understand both normal and abnormal hearts.”
The team plans to provide analysis of samples from animal models and patients with muscle disease to further investigate and understand diseases and develop innovative therapies.
