This award will support collaborative research between Professor Roger Craig of the University of Massachusetts Medical School and Professor Raul Padron of the Instituto Venezolano de Investigaciones Cientificas (IVIC) in Caracas, Venezuela. The objective of this research is to study the structural mechanism of contractile cells in muscle and nonmuscle tissue. These cells are able to contract by the sliding of contractile filaments past one another without any change in filament length. The sliding force is generated by the cyclic interaction of myosin crossbridges with actin filaments and is powered by the splitting of ATP during each crossbridge cycle. Using ultrarapid freezing techniques, the investigators are able to arrest the crossbridges at transient points in the cycle and directly examine, via an electron microscope, intermediate crossbridge states. The physiological techniques and apparatus for freezing the muscles, as well as the facilities and expertise for image processing of the micrographs will be done at IVIC while the U.S. side will carry out most of the freezing and the subsequent electron microscopy of the samples. This research should provide insights into the molecular basis of cellular movement and a better understanding defects in structure that occur in diseased states.
