肌肉收缩Hill特性式的理论研究

从肌球蛋白工作循环的机械化学偶联模型出发,利用化学动力学方法和生化热力学原理,结合肌球蛋白单分子实验结果,从能量转化的角度,研究了肌肉收缩过程中的力与速度关系,发现结果与Hill特性式基本一致。     

果蝇非常规肌球蛋白的结构与功能

肌球蛋白是一类重要的分子马达,可以将ATP水解产生的能量转化成动能,沿由肌动蛋白组成的细丝运动。肌球蛋白构成一个大的基因家族,在许多细胞活动中起着重要作用,包括肌肉收缩、胞内转运、听觉、视觉等。果蝇基因组有13种肌球蛋白基因,包括2种常规肌球蛋白和11种非常规肌球蛋白。本文综述了近年来果蝇非常规肌球蛋白的研究进展。     

肌动蛋白,肌动蛋白结合蛋白质和细胞运动的研究进展

运动是生命细胞的基本特征之一。肌动蛋白、肌球蛋白和调节蛋白质参与细胞运动和肌肉收缩,籍以完成不同的生理功能。蛋白质的结构生物学、分子遗传学和体外运动分析的应用,阐明了肌动蛋白、肌球蛋白和一些结合蛋白质的氨基酸序列、结合功能域和原子结构,使运动和能量转换可在分子水平上进行探索,促进了运动蛋白质体系的运动及其调节机制和能量转换机制研究的发展。     

肌球蛋白工作循环的机械化学偶联模型

目前在众多的分子马达中对骨骼肌肌球蛋白的研究较多,本文对肌球蛋白的结构、工作循环机制以及单分子动力学性质进行了探索。同时,对各种生化条件下肌纤维的收缩性质进行了测试。将Houdusse和Sweeney给出的机械化学偶联模型简化成一个新的四态模型,通过对定态时肌球蛋白态分布的研究,证明了简化模型的合理性。     

肌球蛋白工作循环的一个新模型

分析总结关于分子马达肌球蛋白的最新研究结果,给出一个新的肌球蛋白工作循环的机械化学偶联模型.从新模型出发,用一组化学动力学方程描述肌肉中大量肌球蛋白的集体工作行为.利用动力学方程的非平衡定态解,并结合Pate和Cooke的实验结果得到了力作为变量的肌肉态方程.理论结果同热力学原理一致,与传统的肌肉收缩理论有一定区别.根据肌肉的特殊结构,对肌肉态方程做了进一步讨论.     

肌肉收缩及自发振动的动力学理论

改变实验条件,肌纤维可发生从收缩到自发振动的相变。为了研究这一现象,引进了描述肌纤维内部弹性成分拉伸长度与张力关系的表达式,利用肌肉态方程并考虑肌纤维的特殊结构,给出了描述肌纤维收缩及自发振动的统一动力学方程。从动力学方程出发,肌纤维自发振动的发生条件得到了自然解释,所给出的振动周期和振动曲线同实验结果相符,并给出了一些新的理论结果。这一工作的意义在于,完成了从肌球蛋白单分子性质、肌纤维组织结构到肌纤维功能的信息整合。     

大鼠快慢肌单纤维肌球蛋白轻链的分析比较

从整块肌肉抽提的肌球蛋白,其轻链类型因肌肉收缩的快慢而有区别,即快肌的肌球蛋白有三条轻链,慢肌的肌球蛋白只有二条轻链(Sarker等,1971;Lowey和Risby,1971),它们分别属于不同的肌球蛋白同功酶,这在鸡(Hoh,1978)和兔(Hoh,1979)都是这样。另外,在神经肌肉的发育过程中,一旦有了神经控制,便使起初只合成快型轻链的肌肉,逐步向合成慢型轻链的慢肌分化(Rubinstein和Kelly,1978)。然而,快肌和慢肌不同的轻链图谱特征,是否也表现在肌纤维的快慢类型上呢?这很少见到报道。我们曾观察到单肌纤维的肌球蛋白有二个成份,它们之间的比值和各自的电泳迁移率可以作为区别二类不同单肌纤维的特征(章生艮、任惠民,1983)。我们认为既然快肌纤维和慢肌纤维的肌球蛋白成份各有特征,那末,单肌纤维的肌球蛋白轻链图谱,当然也应该能反映单肌纤维的快、慢类型了。本文目的就是利用毛细管凝胶电泳对单肌纤维的轻链分析,来探讨这个问题。     

纳米机器——分子马达

介绍了细胞内分子马达的能量转化途径,几种纳米分子马达如驱动蛋白、动力蛋白、肌球蛋白和旋转马达的结构和功能,并展望了分子马达对人类的贡献。     

肌球蛋白磷酸化的研究进展

肌球蛋白是肌原纤维粗丝的组成单位,由多条重链与多条轻链组成,被视为一种分子马达。在肌肉收缩、趋化性胞质分裂、胞引作用、膜泡运输以及信号传导等生理过程中起重要作用。目前肌球蛋白磷酸化是研究的一个热点,它对细胞的迁移、收缩、胞质分裂以及其他未知功能都有着至关重要的作用。肌球蛋白磷酸化分为重链的磷酸化与轻链的磷酸化。根据国内外的最新相关研究报道,分别从肌球蛋白的结构与功能、磷酸化的作用机制、磷酸化的生物学功能以及最新研究成果等方面,对肌球蛋白的磷酸化研究进展进行阐述。     

用免疫酶标技术对东方蝾螈胚胎肌肉原肌球蛋白生成时期和部位的观察

原肌球蛋白(Tropomyosin,以下简称TM)是肌肉的结构蛋白之一,它与肌钙蛋白配合,在调节肌肉收缩的过程中起着重要的作用。对于TM的化学结构、免疫学性质及其在肌肉收缩过程中的功能,已有不少研究。一些作者研究了离体培养的成肌细胞在分化时TM的生成和积累。但用免疫组织化学方法,研究TM在胚胎发育过程中的生成和定位方面的工作还不     

Striated Muscle Regulation of Isometric Tension by Multiple Equilibria

Cooperative activation of striated muscle by calcium is based on the movement of tropomyosin described by the steric blocking theory of muscle contraction. Presently, the Hill model stands alone in reproducing both myosin binding data and a sigmoidal-shaped curve characteristic of calcium activation (Hill TL (1983) Two elementary models for the regulation of skeletal muscle contraction by calcium. Biophys J 44: 383–396.). However, the free myosin is assumed to be fixed by the muscle lattice and the cooperative mechanism is based on calcium-dependent interactions between nearest neighbor tropomyosin subunits, which has yet to be validated. As a result, no comprehensive model has been shown capable of fitting actual tension data from striated muscle. We show how variable free myosin is a selective advantage for activating the muscle and describe a mechanism by which a conformational change in tropomyosin propagates free myosin given constant total myosin. This mechanism requires actin, tropomyosin, and filamentous myosin but is independent of troponin. Hence, it will work equally well with striated, smooth and non-muscle contractile systems. Results of simulations with and without data are consistent with a strand of tropomyosin composed of ∼20 subunits being moved by the concerted action of 3–5 myosin heads, which compares favorably with the predicted length of tropomyosin in the overlap region of thick and thin filaments. We demonstrate that our model fits both equilibrium myosin binding data and steady-state calcium-dependent tension data and show how both the steepness of the response and the sensitivity to calcium can be regulated by the actin-troponin interaction. The model simulates non-cooperative calcium binding both in the presence and absence of strong binding myosin as has been observed. Thus, a comprehensive model based on three well-described interactions with actin, namely, actin-troponin, actin-tropomyosin, and actin-myosin can explain the cooperative calcium activation of striated muscle.     

A model of muscle contraction based on the Langevin equation with actomyosin potentials

We propose a muscle contraction model that is essentially a model of the motion of myosin motors as described by a Langevin equation. This model involves one-dimensional numerical calculations wherein the total force is the sum of a viscous force proportional to the myosin head velocity, a white Gaussian noise produced by random forces and other potential forces originating from the actomyosin structure and intra-molecular charges. We calculate the velocity of a single myosin on an actin filament to be 4.9–49 μm/s, depending on the viscosity between the actomyosin molecules. A myosin filament with a hundred myosin heads is used to simulate the contractions of a half-sarcomere within the skeletal muscle. The force response due to a quick release in the isometric contraction is simulated using a process wherein crossbridges are changed forcibly from one state to another. In contrast, the force response to a quick stretch is simulated using purely mechanical characteristics. We simulate the force–velocity relation and energy efficiency in the isotonic contraction and adenosine triphosphate consumption. The simulation results are in good agreement with the experimental results. We show that the Langevin equation for the actomyosin potentials can be modified statistically to become an existing muscle model that uses Maxwell elements.     

Hill's equation applied to reconstituted contractile collagen.

A new type of automatic force-displacement recording myograph has been developed to measure the contraction–relaxation characteristics of contractile systems. The device produces a polytonic (variable-force) load and therefore provides a more realistic measurement than either isometric or isotonic apparatus. Measurements on collagen that was first well ground and then extruded into a reconstituted thin tape show contraction and relaxation behaviour that can be characterized by a slightly modified form of Hill's 1938 equation. The characteristic parameters of the Hill equation determined for the reconstituted collagen were remarkably similar to those of intact muscle tissue.     

肌肉收缩的理论研究

基于肌球蛋白工作循环模型,从物理学的角度出发,利用化学动力学方法,给出肌动蛋白丝的动力学方程,讨论肌球蛋白的运力学行为,发现肌动蛋白运动呈锯齿状,并得到振动周期约为3.0s,与实验结果基本吻合。结论是宏观的肌肉运动是单分子运动的集体协同行为,为肌肉的运动训练和治疗提供理论参考。     

A modified distance variable for the Hill formalism for kinetic models of muscle contraction

The distance variable of the Hill formalism for kinetic models of muscle contraction is compared to a modified distance variable. Instead of measuring the distance from a fixed point on the myosin filament to a neighboring actin, the modified variable measures the deviation of the myosin cross-bridge from its equilibrium position. Although for attached cross-bridges the two definitions are equivalent, the new variable is an index of cross-bridge conformation for cross-bridges of all states. The modified variable may be used to complement the use of the Hill variable, or to replace it. The utility of the modified variable is illustrated by an example which matches cross-bridge structures to biochemical kinetic data and to the free energy functions necessary for the design of a kinetic model.     

On the mechanism of muscular contraction.

A thermodynamic analysis is presented for the energy conversion by muscle contraction. During the cyclic processes the major change in energy of the myosin-actin system is due to bond formation between myosin heads and actin. To account for the high efficiency of a working muscle the work done is connected directly to the formation of myosin-actin bond. It is suggested that successively stronger bonds are formed by a stepwise movement of myosin heads over an interval between two troponin molecules on the actin filament. At the end of the interval, where the bond has maximum strength, energy is supplied to break the bond. Here the work is not primarily connected to the 45 degrees rotation of myosin heads as is commonly done. A way of separating the different kinds of energy losses is presented.     

An "active enzyme" muscle model

A new model of skeletal muscle contraction is presented from a unified view of muscle physiology, chemical energetics and newly obtained experimental data concerning actomyosin ATPase in vitro.In this model an interaction between actin and myosin, involving two distinct active sites, is considered to be the essential elementary mechanism for muscle contractions. These two sites are located on myosin. One site, forming a myosin-ADP-P, complex, has stored energy derived from ATP splitting before the beginning of a contraction. Another site, forming a myosin-ATP complex, upon interacting with actin, catalyzes ATP hydrolysis, using a fraction of the stored energy. The hydrolysis at the latter site is responsible for tension development, while the stored energy is released to drive the contractile reaction between actin and myosin unidirectionally. (Thus, the two sites act co-operatively and they can be viewed as forming an active enzyme.)There has been a difficulty in explaining the shortening heat production with apparent lack of corresponding chemical change at the early stage of contraction. The active enzyme model accounts for the shortening heat as the irreversible release of the stored energy. The heat production appears to precede its corresponding ATP splitting for “refueling” which occurs after complete exhaustion of the stored energy, while the actomyosin ATP hydrolysis takes place proportionally to the work. At the macroscopic level, the model is compatible with Hill's tension-velocity and heat relation.