骨骼肌收缩的多尺度研究

发布时间：2018-03-23 07:15

本文选题：肌节收缩　切入点：肌球蛋白　出处：《浙江大学》2017年博士论文　论文类型：学位论文

【摘要】：肌节作为骨骼肌的结构和功能单元,主要由粗肌丝和细肌丝构成,粗肌丝上伸出多个II型肌球蛋白。在骨骼肌收缩时,肌球蛋白会周期性地结合于细肌丝,并对其施加力作用,致使肌丝间会发生相对滑动。对骨骼肌收缩进行定量研究,有助于理解力对肌球蛋白工作的影响;有助于认识分子马达间的协调作用;有助于加深对分子马达工作机制的认识;有助于促进对分子马达参与的诸多细胞活动的研究,如细胞分裂、纤毛摆动、细胞机械感知和细胞内物质运输等。本文利用理论建模与数值模拟方法对骨骼肌收缩进行多尺度研究,工作或可以用于设计高能量转换率的人工马达。主要研究内容有:(1)利用肌节收缩的稳态模型,对不同情形下的肌节收缩过程进行模拟。研究ATP水解脱开方式和断键脱开方式对工作肌球蛋白力的调节作用。模拟结果表明,在肌球蛋白仅可通过ATP水解方式从细肌丝脱开时,工作肌球蛋白的数目随着外力的增大而增多,此时工作肌球蛋白上的力近乎不变,呈现力稳态现象。在肌球蛋白仅能通过逆锁键断键方式从细肌丝脱开时,工作肌球蛋白的数目不能得到很好的调节,此时肌球蛋白上的力随着外力的增大而增大,表明肌球蛋白的力稳态现象与逆锁键的存在无关。(2)结合肌球蛋白的结构,发展肌球蛋白的瞬态模型,研究肌球蛋白的做功过程,讨论温度对肌球蛋白做功的影响。结果表明,肌球蛋白上的力与滑移距离间呈双线性关系,在肌节收缩时,做功过程中肌球蛋白上的力近乎不变,做功结束后肌球蛋白上的力随着滑移距离的增大而线性减小。随着温度的升高,肌球蛋白的等长肌力会增大,等张收缩长度会下降,而肌球蛋白可释放的弹性能却近乎不变。(3)利用肌球蛋白的状态转换模型,分析肌球蛋白的脱开方式,计算肌球蛋白不同脱开方式的脱开速率。结果表明,肌球蛋白的状态转换和断键间存在耦合性,由于状态转换速率要高于肌球蛋白的断键速率,致使实验所测得肌球蛋白脱开速率较高。(4)结合肌球蛋白做功的瞬态模型,建立肌节收缩的瞬态理论,研究肌球蛋白做功过程对肌节收缩的影响,建立肌球蛋白行为与肌节行为之间的联系。在模型中考虑肌球蛋白断键方式,研究断键方式的存在对肌节收缩速度、工作肌球蛋白数目和工作肌球蛋白上力的影响。肌节收缩瞬态模型下肌节收缩速度、工作肌球蛋白数目和其上的力随外力的变化趋势与实验结果相近,随着外力的增大,肌节收缩速度减小,工作肌球蛋白的数目增多,工作肌球蛋白上的力近乎不变。结果表明瞬态模型能较好地模拟肌节收缩,可用于进一步的瞬态过程研究,如模拟肌节收缩的力瞬态过程和速度瞬态过程;模拟应力纤维对基体刚度的感知过程等。
[Abstract]:As the structural and functional unit of skeletal muscle, sarcomere is mainly composed of coarse muscle silk and fine muscle filament, and more than one type II myosin is projected from the coarse muscle filament. When skeletal muscle contracts, myosin periodically binds to fine muscle filament and exerts force on it. The quantitative study of skeletal muscle contraction is helpful to understand the effect of myosin on myosin work, to understand the coordination between molecular motors, to deepen the understanding of the working mechanism of molecular motors, to cause relative slippage between myofilaments, to study quantitatively the contraction of skeletal muscles, and to understand the effects of myosin on myosin work. Contribute to the study of the many cellular activities in which molecular motors are involved, such as cell division, cilia swing, Cellular mechanical perception and intracellular material transport. In this paper, a multi-scale study of skeletal muscle contraction was carried out using theoretical modeling and numerical simulation. Work may be used to design artificial motors with high energy conversion rates. The effects of ATP hydrolysis and bond breaking on the working myosin force were studied. The simulation results showed that myosin could be removed from the fine muscle filament only by ATP hydrolysis. The number of working myosin increases with the increase of external force, and the force on the working myosin is almost invariable, showing a steady force phenomenon. The number of working myosin can not be adjusted well, and the force on myosin increases with the increase of external force, indicating that the force steady-state phenomenon of myosin has nothing to do with the existence of inverse locking bond. The transient model of myosin is developed, the working process of myosin is studied, and the effect of temperature on the work of myosin is discussed. The results show that the force on myosin has a bilinear relationship with the slip distance. The force on myosin is almost unchanged during work, and the force on myosin decreases linearly with the increase of slip distance after the work is finished. With the increase of temperature, the equal length myosin force increases, and the iso-tensional contraction length decreases. However, the elastic energy released by myosin is almost invariable. (3) using the state transition model of myosin, we analyze the mode of release of myosin and calculate the rate of release of myosin in different ways. The results show that, There is coupling between state transition and broken bond of myosin. Because the rate of state transition is higher than that of myosin, the experimental results show that the rate of myosin de-opening is higher than that of myosin, and the transient model of myosin work is combined with myosin. To establish the transient theory of myosome contraction, to study the effect of myosin work on the contraction of myosome, and to establish the relationship between myosin behavior and sarcomere behavior. To study the effect of bond breaking mode on the contraction velocity, the number of working myosin and the working myosin force. The number of working myosin and the force on the working myosin were similar to the experimental results. With the increase of the external force, the contraction speed of myosin decreased and the number of working myosin increased. The results show that the transient model can simulate the contraction of sarcomere, and can be used to study the transient process of myosin, such as force transient process and velocity transient process. Simulate the sensing process of stress fiber to matrix stiffness, etc.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：Q445

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