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Updated: Jun 25, 2025

Probing Myosin Ensemble Mechanics in Actin Filament Bundles Using Optical Tweezers
Published on: May 4, 2022
Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament
Anthony L Hessel1, Michel N Kuehn2, Seong-Won Han2
1Institute of Physiology II, University of Muenster, Muenster, Germany. anthony.hessel@uni-muenster.de.
Abstract:
In striated muscle, the sarcomeric protein myosin-binding protein-C (MyBP-C) is bound to the myosin thick filament and is predicted to stabilize myosin heads in a docked position against the thick filament, which limits crossbridge formation. Here, we use the homozygous Mybpc2 knockout (C2-/-) mouse line to remove the fast-isoform MyBP-C from fast skeletal muscle and then conduct mechanical functional studies in parallel with small-angle X-ray diffraction to evaluate the myofilament structure. We report that C2-/- fibers present deficits in force production and calcium sensitivity. Structurally, passive C2-/- fibers present altered sarcomere length-independent and -dependent regulation of myosin head conformations, with a shift of myosin heads towards actin. At shorter sarcomere lengths, the thin filament is axially extended in C2-/-, which we hypothesize is due to increased numbers of low-level crossbridges. These findings provide testable mechanisms to explain the etiology of debilitating diseases associated with MyBP-C.
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