SGER: Is titin a "winding filament"? A new twist on muscle contraction
SGER:titin 是一种“缠绕丝”吗?
基本信息
- 批准号:0732949
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-08-15 至 2008-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Despite its huge success, the sliding filament theory of muscle contraction has proven insufficient to explain several long-known and important aspects of muscle function, including: 1) enhancement of force with stretch, 2) depression of force with shortening, 3) the low cost of force production during active stretch, and 4) the high thermodynamic efficiency of actively shortening muscle. Efforts to explain these properties have led to numerous alternative hypotheses. Recent studies have suggested that the giant protein titin may function as a spring in active striated muscle. The important question that remains is whether a titin spring might play a direct role in contraction of calcium-activated muscle, and if so, how? The 'winding filament' model provides a simple and comprehensive mechanism by which titin contributes to muscle contraction. It postulates that titin binds to the thin filament in calcium-activated sarcomeres. Ca2+-dependent binding of titin to the thin filament prevents low-force straightening of titin that normally occurs upon passive stretch of skeletal myofibrils at slack length, and explains differences between cardiac and skeletal muscle in the length-dependence of active force. Because titin is bound to both the thick and thin filaments, rotation of the thin filament by the cross bridges will wind titin upon the thin filament. Winding of titin on the thin filament will store elastic potential energy in unbound titin by increasing its strain and stiffness during isometric force development. The magnitude of changes in strain and stiffness of titin due to thin filament rotation will depend on the winding angle of titin. The elastic energy stored in titin during isometric force development is recovered during active shortening, increasing shortening velocity and power output. The winding filament model has the potential to revolutionize the field of muscle physiology, as well as mathematical and biomechanical models of muscle function, influencing the design of actuators and prostheses, perhaps even artificial hearts.The goal of the proposed research is to develop and test the hypothesis that winding of titin upon the thin filament contributes to muscle force development and active shortening. That goal will be accomplished via three objectives. (1) Continue experimental work to develop, refine, and test predictions of the model. (2) Collaborate with mechanical engineers to develop self-stabilizing actuators based on the winding filament model. (3) Develop new collaborations to test the winding filament model using nanotechnology, to create mathematical and physical models based on the winding filament concept, and to collaborate with industry to develop and manufacture self-stabilizing actuators for applications in robotics and prosthetics. The broader impacts of this proposal include the development of interdisciplinary collaborations among biologists, mathematicians, mechanical engineers, and industry. The proposed studies have the potential to benefit society by facilitating the development of lightweight actuators with properties that closely resemble those of active muscle, including self-stabilization during perturbations in load. Underrepresented students, especially Hispanic and Native American students, will participate as intellectual partners in the proposed studies. The results of this research will be disseminated to a broad audience by publishing in diverse media and by participating in interdisciplinary conferences in the areas of neuroscience, engineering, and mathematics.
尽管肌肉收缩的滑动细丝理论取得了巨大的成功,但已被证明不足以解释肌肉功能的几个长期已知和重要的方面,包括:1)拉伸力的增强,2)缩短力的抑制,3)主动拉伸期间力产生的低成本,以及4)主动缩短肌肉的高热力学效率。为了解释这些特性,人们提出了许多不同的假设。最近的研究表明,巨大的蛋白质肌联蛋白可能作为一个弹簧在活跃的横纹肌。剩下的重要问题是,肌联蛋白弹簧是否可能在钙激活肌肉的收缩中发挥直接作用,如果是这样,又是如何发挥作用的?“缠绕细丝”模型提供了肌联蛋白促进肌肉收缩的简单而全面的机制。它假定肌联蛋白与钙激活的肌节中的细丝结合。钙依赖性结合肌联蛋白的细丝,防止低力拉直肌联蛋白,通常发生在被动拉伸骨骼肌原纤维在松弛长度,并解释了心肌和骨骼肌之间的差异,在长度依赖性的主动力。因为肌联蛋白与粗丝和细丝都结合,所以细丝通过横桥的旋转将肌联蛋白缠绕在细丝上。肌联蛋白在细丝上的缠绕将通过在等长力发展期间增加其应变和刚度来在未结合的肌联蛋白中存储弹性势能。由于细丝旋转而引起的肌联蛋白的应变和刚度的变化幅度将取决于肌联蛋白的缠绕角度。在等长收缩力发展过程中储存在肌联蛋白中的弹性能在主动缩短过程中恢复,增加缩短速度和功率输出。缠绕细丝模型有可能彻底改变肌肉生理学领域,以及肌肉功能的数学和生物力学模型,影响执行器和假体的设计,甚至可能是人工hearts.The拟议研究的目标是开发和测试的假设,肌联蛋白上的细丝缠绕有助于肌肉力量的发展和主动缩短。这一目标将通过三个目标来实现。(1)继续实验工作,以发展,完善和测试模型的预测。(2)与机械工程师合作开发基于缠绕细丝模型的自稳定执行器。(3)开发新的合作,使用纳米技术测试缠绕细丝模型,创建基于缠绕细丝概念的数学和物理模型,并与工业界合作开发和制造用于机器人和假肢应用的自稳定致动器。这一提议的更广泛影响包括生物学家、数学家、机械工程师和工业界之间跨学科合作的发展。拟议的研究有可能通过促进具有与活动肌肉非常相似的特性的轻质致动器的开发来造福社会,包括在负载扰动期间的自稳定。代表性不足的学生,特别是西班牙裔和美洲原住民学生,将作为智力合作伙伴参加拟议的研究。这项研究的结果将通过在各种媒体上发表和参加神经科学,工程和数学领域的跨学科会议来传播给广大受众。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kiisa Nishikawa其他文献
Balance and Its Relation With Different Walking Conditions in Persons Poststroke
- DOI:
10.1016/j.apmr.2019.08.025 - 发表时间:
2019-10-01 - 期刊:
- 影响因子:
- 作者:
Thomas Huck;Tarang Jain;Kiisa Nishikawa - 通讯作者:
Kiisa Nishikawa
Calcium Dependent Interaction Between N2A-Halo and F-Actin: A Single Molecule Study
- DOI:
10.1016/j.bpj.2017.11.1965 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Samrat Dutta;Brent Nelson;Matthew Gage;Kiisa Nishikawa - 通讯作者:
Kiisa Nishikawa
Kiisa Nishikawa的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kiisa Nishikawa', 18)}}的其他基金
Collaborative Research: Deconstructing the contributions of muscle intrinsic mechanics to control of locomotion using a novel Muscle Avatar approach
合作研究:使用新颖的肌肉化身方法解构肌肉内在力学对运动控制的贡献
- 批准号:
2016054 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Standard Grant
PFI: AIR-TT: Preflex versus Reflex Control of a Multijoint Robotic Exoskeleton
PFI:AIR-TT:多关节机器人外骨骼的预反射与反射控制
- 批准号:
1701230 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Standard Grant
Collaborative Research: A New Twist on Muscle Contraction
合作研究:肌肉收缩的新转折
- 批准号:
1456868 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Continuing Grant
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 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Continuing Grant
Collaborative Research: Neural and mechanical bases of motor primitives in voluntary frog behavior
合作研究:青蛙自愿行为中运动原语的神经和机械基础
- 批准号:
0827688 - 财政年份:2008
- 资助金额:
-- - 项目类别:
Continuing Grant
Neuromechanical Control of Elastic Energy Storage and Recovery during Ballistic Movements
弹道运动期间弹性能量存储和恢复的神经机械控制
- 批准号:
0623791 - 财政年份:2006
- 资助金额:
-- - 项目类别:
Continuing Grant
Shortening velocity and power output of muscles that produce ballistic movements
缩短产生弹道运动的肌肉的速度和功率输出
- 批准号:
0240349 - 财政年份:2003
- 资助金额:
-- - 项目类别:
Standard Grant
Biomechanics and Neural Control of Ballistic Tongue Projection
弹道舌投射的生物力学和神经控制
- 批准号:
0215438 - 财政年份:2002
- 资助金额:
-- - 项目类别:
Standard Grant
Musculoskeletal Design, Muscle Activity and Movement
肌肉骨骼设计、肌肉活动和运动
- 批准号:
9507479 - 财政年份:1995
- 资助金额:
-- - 项目类别:
Standard Grant
相似国自然基金
ALKBH5介导的Titin基因调控通过激活Wntβ-catenin信号通路在宫颈癌侵袭和转移中的功能及分子机制研究
- 批准号:
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
相似海外基金
筋傷害バイオマーカーTITINを用いた神経筋電気刺激療法強度に関する無作為化比較試験
使用肌肉损伤生物标志物 TITIN 进行神经肌肉电刺激治疗强度的随机对照试验
- 批准号:
24K19497 - 财政年份:2024
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
球脊髄性筋萎縮症における超早期バイオマーカーの開発
脊髓和延髓肌萎缩症超早期生物标志物的开发
- 批准号:
23K06962 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of strategies to enhance titin (TTN) expression and treat dilated cardiomyopathy caused by TTN haploinsufficiency
开发增强肌联蛋白 (TTN) 表达并治疗 TTN 单倍体不足引起的扩张型心肌病的策略
- 批准号:
10662742 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Titin-based stiffness regulation and mechanosensing in activated skeletal muscle.
激活骨骼肌中基于肌联蛋白的刚度调节和机械传感。
- 批准号:
10751746 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Personalized drug safety and targeted drug therapies for individuals with truncating titin variants
针对肌联蛋白截短变异个体的个性化药物安全性和靶向药物治疗
- 批准号:
490221 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Operating Grants
Impact of titin post-translational modifications on muscle contractile function
肌动蛋白翻译后修饰对肌肉收缩功能的影响
- 批准号:
RGPIN-2019-06609 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Discovery Grants Program - Individual
Establishing and reversing the functional consequences of Titin truncation mutations
建立并逆转肌联蛋白截断突变的功能后果
- 批准号:
10510011 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Establishing and reversing the functional consequences of Titin truncation mutations
建立并逆转肌联蛋白截断突变的功能后果
- 批准号:
10640157 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Designing and Understanding High-performance Titin Polymers Using Synthetic Biology
利用合成生物学设计和理解高性能肌联蛋白聚合物
- 批准号:
2207879 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Standard Grant
Titin isoforms changes following a HIT protocol in the rabbit model
在兔模型中,Titin 异构体按照 HIT 方案发生变化
- 批准号:
563813-2021 - 财政年份:2021
- 资助金额:
-- - 项目类别:
University Undergraduate Student Research Awards