The long-term objective of this research is to reach a detailed understanding of the molecular mechanism of muscle contraction, and at the same time to gain thereby important information about other cellular motile processes involving actin-myosin interactions. Understanding of muscle pathology must remain incomplete until we understand fully the basic mechanism which all the other ancillary processes in muscle cells have to support; a full understanding of cell movements during development, and of cell invasiveness, also requires basic knowledge of the motile mechanisms involved.
The specific aim of the project is to obtain as much information as possible about the structural changes taking place in the myosin crossbridges in muscle as they interact with actin to produce the sliding force between the arrays of actin and myosin filaments. The techniques that will be employed in this work are those of low angle X-ray diffraction and electron-microscopy. The X-ray work will exploit the new sources of high intensity synchrotron radiation at such places as the Brookhaven National Laboratory to carry out detailed time-resolved studies of the changes in the muscle diffraction pattern which reflect the structural events in contraction. The electron-microscope work will make use of rapid freezing techniques to obtain direct images of muscle filaments and crossbridges in chosen states of contraction. Both approaches call for substantial technical developments but, if successful, these new techniques will be of considerable value in other biological fields. The results of these structural studies should provide a detailed framework of understanding for the very active research on contraction and motility being pursued by many other workers using biochemical, biophysical, genetical and physiological techniques.
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| Sosa, H; Popp, D; Ouyang, G et al. (1994) Ultrastructure of skeletal muscle fibers studied by a plunge quick freezing method: myofilament lengths. Biophys J 67:283-92 |
| Huxley, H E; Stewart, A; Sosa, H et al. (1994) X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. Biophys J 67:2411-21 |
