The molecular mechanism of muscle contraction

University Of Florence, Florence

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Abstract

DESCRIPTION (provided by applicant): The aim of this project is to describe at the molecular level how the interaction between actin and myosin generates force and shortening in muscle. We will achieve this by time-resolved X-ray interference measurements on isolated intact fibres from skeletal muscle using the BioCAT beamline at the Advanced Photon Source. The combination of our fast sarcomere-level mechanical techniques with the world-leading facility for muscle X-ray scattering measurements provides a unique opportunity to answer fundamental outstanding questions about the in situ mechanism of the myosin motor. We will focus on four questions: the size of the force-generating working stroke in the motor and its load-dependence; the conformations of myosin heads during steady shortening and the basis of the force-velocity relation in muscle; the myosin head conformations during steady stretch and the mechanisms by which muscle resists active stretch; the factors that determine the isometric force. The answers to these questions are essential for relating molecular and cellular studies of myosin motors, and for elucidating the mechanism of efficient mechanochemical coupling. The results will be significant for understanding the physiology and pathology of skeletal, cardiac and smooth muscles, and the many other cell functions that are driven by myosin motors. [Our research programme will develop hardware, software and expertise of BioCAT beam line that can subsequently be used by US-based muscle researchers.]