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Macromolecular modelling of muscle structure : a comparison with x-ray diffraction results

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posted on 2014-12-15, 10:40 authored by Catherine V. Miles
During contraction, the molecular arrangement within muscle undergoes large changes which can be traced through corresponding changes in the x-ray diffraction patterns. This thesis investigates the relationship between changes in the muscle structure and those in the resulting diffraction patterns, in order to shed light on the contractile cycle itself.;High resolution x-ray diffraction patterns were obtained from whole frog sartorius muscles using synchrotron radiation. The patterns were obtained at three stages of the contractile cycle: rest, isometric contraction and unloaded shortening.;Three-dimensional computer models were built from the main components of muscle: the proteins actin and myosin arranged in helical filaments. The specific positions and orientations of the protein components were adjusted until the main features of the resulting theoretical diffraction pattern matched those of the experimental x-ray diffraction patterns.;The results of this study indicated that in rest muscle the main mass of the myosin head lies parallel to the muscle's long axis, and the heads are wrapped around the thick filament from which they protrude forming a compact structure. Introducing disorder into the molecular arrangement revealed that a high degree of azimuthal disorder in the myosin head arrangement was required to reproduce the pattern from isometrically contracting muscle. During unloaded shortening axial filament disorder was the prime candidate.;The main focus of this study was the arrangement of myosin molecules in the thick filaments, but initial studies of the arrangement of actin monomers in the thin filaments indicated that a random cumulative disorder of 10° r.m.s. is present in the helical arrangement of the actin monomers..

History

Date of award

1997-01-01

Author affiliation

Physics

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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