Cardiac muscle architecture in health and disease

Survival and health in vertebrates and humans is ensured by the continuous operation of the heart. In turn, the function of the cardiac and skeletal muscle relies on the sarcomere, the smallest cellular unit capable of contraction. Understanding the molecular mechanisms that underlie sarcomere regulation and function is therefore vital for a healthy heart.

Seeking to address this, the EU-funded MUZIC (Muscle Z-disk protein complexes: from atomic structure to physiological function) project set out to investigate the specific muscle sarcomere compartment known as the Z-disk. The Z-disk provides the attachment region for neighbouring sarcomere units and therefore plays a pivotal role in maintaining muscle architecture.

Through a multi-disciplinary approach, MUZIC project partners set out to generate a comprehensive spatio-temporal picture of the muscle Z-disk protein complexes. They focused on the atomic structure of selected components central to Z-disk integrity and studied their architecture and interacting partners. In addition, they analysed the cellular mechanisms that are involved in the function, dynamics, and regulation of the Z-disk. The analysis enabled scientists to elucidate the dynamic changes involved in Z-disk regulation, addressing both the atomic structure and function in health and disease.

The training programme included numerous scientific workshops, complementary skills workshops and a summer school based on basic fluorescence microscopy. The project concluded with an international conference entitled 'Myofibrillar Z-disk Structure and Dynamics'.

Apart from fundamental knowledge, the information generated during MUZIC provided insight into the Z-disk development and remodelling. Consideration of this novel data into the design of therapeutic interventions might improve heart function.