title: The myosin motor in muscle generates a smaller and slower working stroke at higher load.
abstract: Muscle contraction is driven by the motor protein myosin II, which binds transiently to an actin filament, generates a unitary filament displacement or 'working stroke', then detaches and repeats the cycle. The stroke size has been measured previously using isolated myosin II molecules at low load, with rather variable results, but not at the higher loads that the motor works against during muscle contraction. Here we used a novel X-ray-interference technique to measure the working stroke of myosin II at constant load in an intact muscle cell, preserving the native structure and function of the motor. We show that the stroke is smaller and slower at higher load. The stroke size at low load is likely to be set by a structural limit; at higher loads, the motor detaches from actin before reaching this limit. The load dependence of the myosin II stroke is the primary molecular determinant of the mechanical performance and efficiency of skeletal muscle.
authors.affiliation: Laboratorio di Fisiologia, DBAG, Università di Firenze, I-50134 Firenze, and OGG, Istituto Nazionale di Fisica della Materia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Reconditi
authors.forename: Marco
authors.initials: M
authors.lastname: Linari
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lucii
authors.forename: Alex
authors.initials: A
authors.lastname: Stewart
authors.forename: Yin-Biao
authors.initials: YB
authors.lastname: Sun
authors.forename: Peter
authors.initials: P
authors.lastname: Boesecke
authors.forename: Theyencheri
authors.initials: T
authors.lastname: Narayanan
authors.forename: Robert F
authors.initials: RF
authors.lastname: Fischetti
authors.forename: Tom
authors.initials: T
authors.lastname: Irving
authors.forename: Gabriella
authors.initials: G
authors.lastname: Piazzesi
authors.forename: Malcom
authors.initials: M
authors.lastname: Irving
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lombardi
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D007537:Isometric Contraction; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D024462:Myosin Type II / Q000737:chemistry / Q000378:metabolism*; D011898:Ranidae; D014965:X-Rays
chemical_list: D020409:Molecular Motor Proteins; D024462:Myosin Type II