Collaborative Research: A New Twist on Muscle Contraction

合作研究：肌肉收缩的新转折

• 批准号: 1456868
• 负责人: Kiisa Nishikawa
• 金额: $ 37.21万
• 依托单位: Northern Arizona University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1456868&HistoricalAwards=false
• 关键词: Collaborative; Research; New; Twist; Muscle

The sliding filament theory is widely accepted as a useful model of muscle contraction in isolated preparations. However, the theory fails to account for critically important characteristics of muscle function. Despite decades of work, a predictive model of muscle force during natural movements remains elusive. The researchers will test the hypothesis that important properties of muscle can be explained by the winding filament hypothesis. The proposed work has significant potential to inform our understanding of how neural activation and applied forces together determine in vivo muscle force. Results from the research will be integrated into graduate and/or undergraduate courses at Denison University (RUI-eligible), Northwestern University, and Northern Arizona University. In addition, the research team will leverage programs at Denison University and Northern Arizona University for recruiting under-represented participants in research. Results will be disseminated to broad audiences through standard mechanisms of publication and diverse public media, as well as participation in interdisciplinary conferences in the areas of engineering, biomechanics, and physiology.The researchers will use the mdm mouse to test predictions of the winding filament hypothesis. The winding hypothesis claims that, in addition to the thin filaments, titin is activated by Ca2+, and that cross-bridges not only translate but also rotate the thin filaments, storing elastic energy in PEVK titin during isometric force development. Due to constraints of sarcomere geometry on titin activation and winding, the hypothesis makes unique quantitative predictions about the effects of stimulation and length changes on muscle force. By including different muscles in the proposed studies, the researchers can determine whether naturally occurring variation in titin structure and function contributes to activation- and length-dependent muscle properties (e.g., doublet potentiation and force depression/enhancement). The experiments will test whether titin activation and winding, alone or in combination, can account for observed muscle forces by comparing experimental results to model predictions.

滑丝理论被广泛接受为一个有用的模型，肌肉收缩在隔离的准备。然而，该理论未能解释肌肉功能的重要特征。尽管经过数十年的研究，自然运动过程中肌肉力量的预测模型仍然难以捉摸。研究人员将测试这一假设，即肌肉的重要特性可以用缠绕细丝假说来解释。拟议的工作有显着的潜力，告知我们的理解如何神经激活和施加的力量一起决定在体内肌肉力量。研究结果将被纳入丹尼森大学（RUI合格），西北大学和北方亚利桑那大学的研究生和/或本科课程。此外，研究小组将利用丹尼森大学和北方亚利桑那大学的项目，招募代表性不足的参与者进行研究。研究结果将通过标准的出版机制和各种公共媒体，以及参加工程学、生物力学和生理学领域的跨学科会议，向广大受众传播。研究人员将使用mdm小鼠来测试缠绕细丝假说的预测。缠绕假说声称，除了细丝，肌联蛋白被Ca 2+激活，并且横桥不仅平移而且旋转细丝，在等长力发展期间在PEVK肌联蛋白中存储弹性能量。由于肌小节的几何形状对肌联蛋白激活和缠绕的限制，该假说对刺激和长度变化对肌肉力量的影响做出了独特的定量预测。通过在拟议的研究中包括不同的肌肉，研究人员可以确定肌联蛋白结构和功能的自然发生的变化是否有助于激活和长度依赖性肌肉特性（例如，双峰增强和力抑制/增强）。这些实验将测试肌联蛋白激活和缠绕，单独或组合，是否可以通过比较实验结果与模型预测来解释观察到的肌肉力量。