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.

滑动丝理论被广泛认为是孤立制剂中肌肉收缩的有用模型。然而，该理论未能解释肌肉功能的极其重要的特征。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。研究人员将验证肌肉的重要特性可以通过缠绕丝假说来解释的假设。这项工作具有巨大的潜力，可以帮助我们理解神经激活和施加的力如何共同决定体内肌肉力量。研究结果将被纳入丹尼森大学（符合 RUI 资格）、西北大学和北亚利桑那大学的研究生和/或本科生课程。此外，研究团队将利用丹尼森大学和北亚利桑那大学的项目来招募代表性不足的研究参与者。研究结果将通过标准的出版机制和多样化的公共媒体以及参与工程、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 鼠标来测试缠绕丝假说的预测。缠绕假说声称，除了细丝之外，肌动蛋白也被 Ca2+ 激活，并且跨桥不仅平移而且旋转细丝，在等长力发展过程中将弹性能储存在 PEVK 肌动蛋白中。由于肌节几何形状对肌蛋白激活和缠绕的限制，该假设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纳入不同的肌肉，研究人员可以确定肌联蛋白结构和功能中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，双联体增强和力抑制/增强）。这些实验将通过将实验结果与模型预测进行比较，测试肌动蛋白激活和缠绕（单独或组合）是否可以解释观察到的肌肉力量。