The long term goal of this project is to provide new insights into the molecular structure of the contractile filaments of muscle and the structural changes that underlie contraction and its regulation.
Specific aims are: (1) to describe the structural changes that occur in myosin crossbridges during their cycle of attachment to actin when a muscle contracts; (2) to define the regulatory structural changes that occur in the contractile filaments when they are activated; (3) to elucidate further the crossbridge arrangement and backbone structure of the myosin filaments of smooth and striated muscles. These questions will be approached using high resolution electron microscopy, combined with image analysis, to elucidate the structures of contractile molecules, filaments and whole muscles in relaxed and activated states. Intact smooth and striated muscle tissue, in the relaxed or contracting state, will be studied by rapid freezing and cryosectioning methods; isolated filaments by negative staining or """"""""frozen hydrated"""""""" methodology combined with minimal electron dose methods; and purified muscle proteins by rotary shadowing. The results of this project should broaden our understanding of the structure of healthy muscle and of the molecular processes underlying contraction and its regulation. Such knowledge is essential to an understanding of defects in structure that occur in diseased states.
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