Structural bases of striated muscle contraction

Muscle contraction is regulated by both Ca2+-dependent thin filament activation and mechanosensing-based thick filament activation, with the involvement of both the cytoskeleton protein titin, which runs from the midpoint of the thick filament to the edge of the sarcomere, and the myosin binding protein C (MyBP-C), bound to the backbone of thick filament in the 1/3 central region of each half and dynamically bridging it to thin filament. Growing evidence indicates titin as the trigger for the thick filament activation through a Ca2+ dependent stiffening of its I-band region, either directly or through attachment to activated thin filament. To clarify this point, we plan to test the effect of MYK-7660, an inhibitor of thin filament activation, on the activation-dependent stiffening of titin, by combining mechanical measurements with X-ray signals marking the regulatory state of thin and thick filaments in frog muscle fibres stimulated both in control and in presence of the inhibitor.