Is Titin an Exponential Spring in Active Muscle?

肌动蛋白是活跃肌肉中的指数弹簧吗？

• 批准号: 1025806
• 负责人: Kiisa Nishikawa
• 金额: $ 77.72万
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1025806&HistoricalAwards=false
• 关键词: Titin; Exponential; Spring; Active; Muscle

During the past century, physiologists have made remarkable progress in elucidating the molecular mechanisms of muscle contraction. Despite this progress, the goal of predicting how muscle force changes during natural movements has remained elusive. This project will advance the understanding of muscle contraction by (1) testing the hypothesis that the length and stiffness of the giant, elastic titin protein changes when calcium is released from the sarcoplasmic reticulum upon muscle activation and (2) developing a computer model of muscle based on this hypothesis. A mutant mouse that carries a deletion in the titin gene will be used to test the hypothesis. This research will involve: (1) gel electrophoresis to estimate molecular weights of titin in mutant genotypes, (2) force-lever experiments to characterize activation-dependent elastic properties of titin in myofibrils, single fibers and whole muscles, (3) development of a muscle model that incorporates calcium activation of titin, and (4) behavioral studies to compare kinematics and energetics of locomotion across mutant genotypes. The broader impacts of this work include: (1) interdisciplinary training of undergraduate, graduate, and post-doctoral scholars in neuroscience, engineering, and computer science, (2) participation of under-represented students, and (3) public outreach including participation in the research project by local High School teachers and students from a public science and technology magnet school. Results will be disseminated through publication in diverse media and participation in interdisciplinary conferences in the areas of computer science, engineering, and biology. This research has the potential to transform our understanding of the process of muscle activation, improve neuro-musculoskeletal simulations, inform causes and potential cures for neuromuscular diseases, and inspire the design of actuators and prostheses that function more like animal muscles.

在过去的一个世纪中，生理学家在阐明肌肉收缩的分子机制方面取得了显着进步。尽管取得了这种进步，但预测自然运动中肌肉力量如何变化的目的仍然难以捉摸。该项目将通过（1）测试以下假设，即巨型弹性滴定蛋白的长度和刚度在肌肉激活后从肌浆网释放出钙时会发生变化的假设，并且（2）基于此假设，开发肌肉的计算机模型。在TITIN基因中携带缺失的突变小鼠将用于检验假设。这项研究将涉及：（1）凝胶电泳以估算突变基因型中替丁的分子量，（2）力杠杆实验，以表征蛋白质中钛的激活依赖性弹性特性，在肌原纤维，单纤维和整个肌肉中，（3）结合肌肉激活的肌肉激活的肌肉模型（3），（3）突变基因型的运动。这项工作的更广泛影响包括：（1）对本科，研究生和博士后学者在神经科学，工程和计算机科学领域的跨学科培训，（2）参与不足的学生，以及（3）包括地方高中教师和公立科学学院的研究项目的公共外展活动，包括参与公共研究项目。结果将通过在各种媒体中的出版物中发表，并参与计算机科学，工程和生物学领域的跨学科会议。这项研究有可能改变我们对肌肉激活过程的理解，改善神经肌肉骨骼模拟，为神经肌肉疾病的原因和潜在的治疗方法提供了信息，并激发了更像动物肌肉的执行器和假体的设计。