U.S.-Venezuela Cooperative Research: Ultrastructure of Contracting Muscle Studied by Rapid Freezing

该奖项将支持马萨诸塞大学医学院的Roger Craig教授和委内瑞拉加拉加斯的委内瑞拉科学研究研究所（IVIC）的Raul Padron教授之间的合作研究。本研究的目的是研究肌肉和非肌肉组织中收缩细胞的结构机制。这些细胞能够通过可收缩的细丝相互滑动而收缩，而不改变细丝的长度。滑动力是由肌凝蛋白交叉桥与肌动蛋白丝的循环相互作用产生的，并由每个交叉桥周期中ATP的分裂提供动力。使用超快速冷冻技术，研究人员能够在循环的瞬态点上捕获交叉桥，并通过电子显微镜直接检查中间交叉桥状态。冷冻肌肉的生理技术和设备，以及显微镜图像处理的设施和专业知识将在IVIC完成，而美国方面将进行大部分冷冻和随后的电子显微镜检查。这项研究将提供对细胞运动的分子基础的见解，并更好地理解在患病状态下发生的结构缺陷。

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.