ANALYSIS OF CROSS-BRIDGE MECHANICS

肌肉收缩研究的一个长期目标是 解释肌肉纤维的生理反应， 肌动球蛋白相互作用的动力学和能量学。 的 拟议的工作将通过测量力学来实现这一目标 单一的，可渗透的，骨骼肌纤维在 各种各样的条件。 这些数据将被用来提炼 的复杂动力学和能量学的数学模型， 收缩相互作用 拟议的研究是一个延续 在过去的6年里， 年 以前的工作已经表征了配体对 快速骨骼纤维的缩短， 慢肌延长法和快慢肌延长法 纤维将产生新的数据，定义MgATP的相互作用， 其他配体与收缩蛋白。 额外 将肌肉生理学与更广为人知的 acto-S1相互作用的生物化学将通过以下方法确定： 比较活性纤维的响应和 使用一系列不同核苷酸的acto-S1相互作用 在核糖环的任一个碱基处修饰。 利用最近 开发的方法，使研究纤维在更高的 温度，以前在10摄氏度进行的研究也将 可以扩展到更多的生理温度， 结果表明，纤维的反应，以改变在 MgATP或pH值可能与在较低温度下发现的那些完全不同。 温度 上述研究中获得的数据将 导致更详细地了解的能量 在底物结合或产物中涉及的交叉脊态 release. 这可能反过来导致更合理的治疗方法， 心血管疾病治疗中的收缩控制 紊乱

One long range goal in the study of muscle contraction is to explain the physiological responses of muscle fibers in terms of the kinetics and energetics of the actomyosin interaction. The proposed work will approach this goal by measuring the mechanics of contraction of single, permeable, skeletal muscle fibers under a variety of conditions. These data will be used to refine mathematical models of the complex kinetics and energetics of the contractile interaction. The proposed studies are a continuation of an extensive series of experiments carried out over the last 6 years. Previous work has characterized the effect of ligands on the shortening of fast skeletal fibers, and an extension of this approach to slow muscle and to lengthening of both fast and slow fibers will produce new data defining the interaction of MgATP and other ligands with the contractile proteins. Additional correlations linking muscle physiology to the more well known biochemistry of the acto-S1 interaction will be determined by comparing the response of active fibers and the kinetics of the acto-S1 interaction using a series of different nucleotides modified at either the base of ribose ring. Using recently developed methods that allow studies of fibers at higher temperatures, previous studies performed at 10 degree C will also be extended to more to physiological temperatures where preliminary results show that the response of the fibers to alterations in MgATP or pH may be quite different from those found at the lower temperature. Together the data obtained in eh above studies will lead to a more detailed understanding of the energetics of the cross-ridge states involved in substrate binding or in product release. This may in turn lead to more rational therapies for the control of contraction in the treatment of cardiovascular disorders.