idw – Informationsdienst Wissenschaft

Nachrichten, Termine, Experten

Grafik: idw-Logo
Thema Corona

Imagefilm
Science Video Project
idw-News App:

AppStore



Share on: 
03/24/2021 21:16

Zooming in on Muscle Cells

Johann Jarzombek Presse- und Öffentlichkeitsarbeit
Max-Planck-Institut für molekulare Physiologie

    Scientists have produced the first high-resolution 3D image of the sarcomere, the basic contractile unit of skeletal and heart muscle cells, by using electron cryo-tomography (cryo-ET). The international team, led by Stefan Raunser, Director at the Max Planck Institute of Molecular Physiology in Dortmund, in collaboration with Mathias Gautel at the King's College in London, describes the findings this week in the online version of the journal Cell. Cryo-ET capability of imaging structures directly in frozen muscle cells could translate into future medical treatments for muscle diseases and a better understanding of the aging process.

    Sarcomeres are small repeating subunits of myofibrils, the long cylinders that bundle together to make the muscle fibres. Inside the sarcomeres, filaments of the proteins myosin and actin interact to generate muscle contraction and relaxation. So far, traditional experimental approaches to investigate the structure and function of muscle tissue were performed on reconstructed protein complexes or suffered from low resolution. “Electron cryo-tomography, instead, allows us to obtain detailed and artefact-free 3D images of the frozen muscle”, says Raunser.

    An old technique flexes its muscles
    Cryo-ET was for a long time an established yet niche methodology. But recent technical advances in electron cryo-microscopy (cryo-EM) as well as the new development of cryo focused ion beam (FIB) milling are pushing cryo-ET resolution. Similar to cryo-EM, researchers flash-freeze the biological sample at a very low temperature (- 175 °C). Through this process, the sample preserves its hydration and fine structure and remains close to its native state. FIB milling is then applied to shave away extra material and obtain an ideal thickness of around 100 nanometers for the transmission electron microscope, which acquires multiple images as the sample is tilted along an axis. Finally, computational methods reconstruct a three-dimensional picture at high resolution.

    Raunser’s team performed cryo-ET on mouse myofibrils isolated at the King's College, and obtained a resolution of one nanometer (a millionth of a millimetre, enough to see fine structures within a protein): “We can now look at a myofibril with details thought unimaginable only four years ago. It’s fascinating!”, says Raunser.

    Fibres in their natural context
    The calculated reconstruction of the myofibrils revealed the three-dimensional organisation of the sarcomere, including the sub regions M-, A-, and I- bands, and the Z-disc, which unexpectedly forms a more irregular mesh and adopts different conformations. The scientists used a sample with myosin strongly bound to actin, representing a stage of the contracting muscle that is called the rigor state. And indeed, they could visualise for the first time in the native cell how two heads of the same myosin bind to an actin filament. They also discovered that the double head not only interacts with the same actin filament but is also found split between two actin filaments. This has never been seen before and shows that proximity to the next actin filament is stronger than the cooperative effect between the neighbouring heads.

    “This is just the beginning. Cryo-ET is moving from niche to widespread technology in structural biology”, says Raunser. “Soon we will be able to investigate muscle diseases at molecular and even atomic level”. Mouse muscles are very similar to those of humans, yet scientists plan to investigate muscle tissue from biopsies or derived from pluripotent stem cells.


    Original publication:

    Wang Z, Grange M, Wagner T, Khoo AL, Gautel M, Raunser S
    The molecular basis for sarcomere organization in vertebrate skeletal muscle. Cell
    https://doi.org/10.1016/j.cell.2021.02.047


    Criteria of this press release:
    Business and commerce, Journalists, Scientists and scholars, Students, Teachers and pupils, all interested persons
    Biology, Chemistry
    transregional, national
    Research results, Scientific Publications
    English


    3D-reconstruction of the sarcomere. Coloured strains show individual filaments.


    For download

    x

    Sarcomere organization at molecular level


    For download

    x

    Help

    Search / advanced search of the idw archives
    Combination of search terms

    You can combine search terms with and, or and/or not, e.g. Philo not logy.

    Brackets

    You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).

    Phrases

    Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.

    Selection criteria

    You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).

    If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).