Mechanism of force generation by myosin heads in skeletal muscle.
Muscles generate force and shortening in a cyclical interaction between the myosin head domains projecting from the myosin filaments and the adjacent actin filaments. Although many features of the dynamic performance of muscle are determined by the rates of attachment and detachment of myosin and actin, the primary event in force generation is thought to be a conformational change or 'working stroke' in the actin-bound myosin head. According to this hypothesis, the working stroke is much faster than attachment or detachment, but can be observed directly in the rapid force transients that follow step displacement of the filaments. Although many studies of the mechanism of muscle contraction have been based on this hypothesis, the alternative view-that the fast force transients are caused by fast components of attachment and detachment--has not been excluded definitively. Here we show that measurements of the axial motions of the myosin heads at ångström resolution by a new X-ray interference technique rule out the rapid attachment/detachment hypothesis, and provide compelling support for the working stroke model of force generation.
Piazzesi
Gabriella
G
Università di Firenze, Viale G.B. Morgagni 63, I-50134 Firenze, Italy.
Reconditi
Massimo
M
Linari
Marco
M
Lucii
Leonardo
L
Sun
Yin-Biao
YB
Narayanan
Theyencheri
T
Boesecke
Peter
P
Lombardi
Vincenzo
V
Irving
Malcolm
M
D000818:Animals; D001696:Biomechanical Phenomena; D066298:In Vitro Techniques; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009218:Myosins / Q000502:physiology*; D011896:Rana temporaria; D014961:X-Ray Diffraction
D020409:Molecular Motor Proteins; D009218:Myosins