Ultrastructural and kinetic evidence support that thick filaments slide through the Z-disc

How myofilaments operate at short mammalian skeletal muscle lengths is unknown. A common assumption is that thick (myosin-containing) filaments get compressed at the Z-disc. We provide ultrastructural evidence of sarcomeres contracting down to 0.44 µm—approximately a quarter of thick filament resting length—in long-lasting contractions while apparently keeping a regular, parallel thick filament arrangement. Sarcomeres produced force at such extremely short lengths. Furthermore, sarcomeres adopted a bimodal length distribution with both modes below lengths where sarcomeres are expected to generate force in classic force–length measurements. Mammalian fibres did not restore resting length but remained short after deactivation, as previously reported for amphibian fibres, and showed increased forces during passive re-elongation. These findings are incompatible with viscoelastic thick filament compression but agree with predictions of a model incorporating thick filament sliding through the Z-disc. This more coherent picture of mechanical mammalian skeletal fibre functioning opens new perspectives on muscle physiology.