Muscles are connected to tendons to power animal movements such as running, swimming or flying. Forces are produced by myofibrils, contractile chains of actin and myosin, which are pulling on muscle-tendon connections called attachments. During animal development, these muscle-tendon attachments must be established such that they resist high mechanical forces for the entire life of the animal. How the individual protein molecules that build the attachments ‘feel’ the mechanical forces inside an intact muscle can now be measured with modern cell and developmental biology techniques.
An interdisciplinary team lead by Frank Schnorrer and Carsten Grashoff at the Developmental Biology Institute of CNRS & Aix Marseille University, the Max Planck Institute of Biochemistry in Munich and the Institute for Molecular Cell Biology at University of Münster has now been able to quantify the mechanical forces transmitted by a key attachment protein called Talin during the development of muscle attachments.
Sandra Lemke, a PhD student in the Schnorrer group, used the flight muscles of the fruit fly Drosophila for these molecular force measurements and found that a surprisingly small proportion of Talin molecules experiences detectable forces at developing muscle-tendon attachments. She found that muscles deal with the increasing tissue forces by recruiting an high number of Talin molecules to attachments. This way, many Talin molecules can dynamically share the high peak forces produced during muscle contractions, for example while flying.
This mechanical adaptation concept ensures that muscle-tendon connections can last for life. These new results have just been published in PLoS Biology.
Integrin-based adhesions are important force sensing structures of animal cells. The integrin receptors sit at the cell surface probing the environment outside the cell and binding to one end of Talin inside the cell. The other end of Talin binds to the contractile actin-myosin cytoskeleton, so Talin is in the perfect location to sense forces. Earlier studies by the Grashoff lab found that 70% of all Talin molecules are exposed to high forces in so called focal adhesions, when cells are placed on hard plastic or glass substrates in the laboratory. Therefore, it is surprising that our new study now found that less than 15% of the Talin molecules feel measurable forces at developing muscle attachments in an intact organism. It is important to know that a muscle connected to tendon cells is in a much softer environment as compared to cells in a hard plastic dish in the laboratory. Yet, developing muscles must anticipate high forces generated during muscle contractions in the future in the adult fly. To prepare for that, muscles recruit many Talin and Integrin molecules. If scientists reduce the Talin accumulation in an experiment by using fly genetics, the flies can live, but their muscle-tendon connections rupture during the first flight attempts, so the flies can no longer fly. These results demonstrate that connections between cells must dynamically adapt to the needs of each tissue to ensure lifelong function. In the future, it will be exciting to explore how mechanical signals achieve the recruitment of the correct number of molecules to the appropriate location in the cells.