Figure 1.

Hierarchical organization of myofibril. (a) Segment of myofibril captured between two microneedles for force measurements or application of length changes. (b) The sarcomere (structure between two Z-discs), with key protein components schematically illustrated. The resting length of the sarcomere is approximately 2.0 μm in the human heart and 2.5 μm in human skeletal muscle. Insets: the thin filament (top); critical molecular arrangement of the Z-disc (middle); extending myosin catalytic domain and lever arm interacting with actin filament (bottom; left) and 4 molecules of myosin subfragment 1 interacting with actin filament in the absence of ATP (PDB 1MQ8; bottom right). Regulatory light chain (RLC) and essential light chain (ELC) stabilize the lever arm. (c) Schematic illustration of myosin molecule (approximately to scale; see also (b)) and soluble motor fragments, heavy meromyosin (HMM) and subfragment 1 (S1) obtained by proteolytic cleavage under different conditions [356, 357].