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.     

The relationship between muscle kinetic parameters and kinematic variables in a complex movement

Kinematic variables of the vertical jump (jumping height, jump phase durations and joint angles) were measured on 39 male physical education students. In addition, kinetic parameters of the hip and knee extensors, and of the plantar flexors (maxima voluntary force and its rate of development) were recorded on the same subjects, in isometric conditions. The results demonstrated significant positive correlations between kinetic parameters of the active muscle groups and jumping height (r = 0.217-0.464). The dominant effect on these correlations was due to the knee extensors. Correlations between these parameters and the duration of the jump phases were much weaker. Correlation coefficients between kinetic parameters and limb angles in the lowest body position showed that fast force production in one muscle group was related to a significant decrease in the joint angles of distant body segments. Multiple correlation coefficients between leg extensor parameters and kinematic variables (ranging between 0.256 for the duration of the counter-movement phase and 0.616 for jump height) suggested that kinetic parameters could explain more than a quarter of the variability of this complex human movement. Therefore, the conclusion was drawn that an extended set of measurements of the relevant musculo-skeletal system parameters could predict a considerable amount of the variability of human movement. However, high correlation coefficients between the same kinetic parameters of different muscle groups suggest that not all active muscle groups have to be included in the measurements.     

Transition state of the glycolytic pathway under FDP saturating conditions: experimental studies and a theoretical model

1. The transition state of the glycolytic pathway, under FDP saturating conditions, from no ADP to ADP-saturating levels, is studied in a metabolic model in vitro obtained from rat skeletal muscle. 2. When ADP is absent from the reaction mixture a steady state for NADH concentration is observed. After ADP addition, a new steady state is reached. The transition state from the first steady state to the second one shows a pulse of NADH. Both the profile and the size of this pulse depend on the enzyme concentration. 3. A kinetic model of the lower part of glycolysis (after PFK reaction) is proposed, and this is described by a set of first order coupled nonlinear differential equations. The results obtained through stability analysis and numerical integration of these equations agree with the experimental ones. 4. The possible role of the above mentioned transition state on the transmitter mechanism of glycolytic oscillations from PFK to the lower part of the glycolysis is discussed.     

The use of metallochromic Ca indicators in skeletal muscle

Absorbance signals recorded with metallochromic indicators in skeletal muscle fibers show rapid time courses that probably closely track the fast kinetic process of Ca++ release and retrapping by the sarcoplasmic reticulum. However, the formation of more than one complex in cuvette calibrations, both for Arsenazo III (ArIII) and Antipyrylazo III (ApIII), suggest that care needs to be taken in the deconvolution of in vivo absorbance signals. Since the kinetic rate constants have not yet been obtained for these probes, attempts to deconvolute absorbance signals should be considered approximate. The evidence suggesting that more than one complex is formed during a skeletal muscle transient with ArIII is more compelling than for the case of ApIII. The differences between the ArIII and ApIII signals may not be readily explained assuming 1:1 dye:Ca complexation and kinetic differences between the probes. Competition for Ca++ with cell Ca buffers and/or multiple complex formation by at least one of these probes needs to be invoked. Based on a simple model to simulate the behavior of the Ca signals in muscle, it may be suggested that an ApIII-like probe would more closely track pCa changes in the fiber than would an ArIII-like probe, which would show more interference with intracellular buffers; an even higher affinity probe would tend to sense the total release of Ca by the SR.     

Evaluation of performance criteria for simulation of submaximal steady-state cycling using a forward dynamic model.

The objectives of this study were twofold. The first was to develop a forward dynamic model of cycling and an optimization framework to simulate pedaling during submaximal steady-state cycling conditions. The second was to use the model and framework to identify the kinetic, kinematic, and muscle timing quantities that should be included in a performance criterion to reproduce natural pedaling mechanics best during these pedaling conditions. To make this identification, kinetic and kinematic data were collected from 6 subjects who pedaled at 90 rpm and 225 W. Intersegmental joint moments were computed using an inverse dynamics technique and the muscle excitation onset and offset were taken from electromyographic (EMG) data collected previously (Neptune et al., 1997). Average cycles and their standard deviations for the various quantities were used to describe normal pedaling mechanics. The model of the bicycle-rider system was driven by 15 muscle actuators per leg. The optimization framework determined both the timing and magnitude of the muscle excitations to simulate pedaling at 90 rpm and 225 W. Using the model and optimization framework, seven performance criteria were evaluated. The criterion that included all of the kinematic and kinetic quantities combined with the EMG timing was the most successful in replicating the experimental data. The close agreement between the simulation results and the experimentally collected kinetic, kinematic, and EMG data gives confidence in the model to investigate individual muscle coordination during submaximal steady-state pedaling conditions from a theoretical perspective, which to date has only been performed experimentally.     

Steady-state kinetics of coupled two-enzyme reactor with recycling of poly(ethylene glycol)-bound NAD

The kinetic properties of a continuous enzyme reactor containing rabbit muscle lactate dehydrogenase, horse liver alcohol dehydrogenase and poly(ethylene glycol)-bound NAD (PEG-NAD) were investigated experimentally and theoretically. The enzymes and PEG-NAD were retained in the reactor with an ultrafiltration membrane, and the substrates (pyruvate and ethanol) were fed continuously. The reactions of the dehydrogenases were coupled by the recycling of the cofactor. The steady-state concentration of L-lactate, one of the products, was measured under different experimental conditions and compared with the corresponding theoretical value. The theoretical value was calculated based on a simplified ordered bi-bi mechanism for the individual enzyme reactions, of which kinetic constants were determined by independent kinetic studies. Differences were found between the kinetic constants of the enzymes for NAD(H) and PEG-NAD(H). The steady-state values obtained by continuous operation were lower than those calculated, possibly due to the simplification made for the kinetic model; but there was general agreement between them in the dependence on the experimental conditions. The steady-state behavior of the enzyme reactor was explained semi-quantitatively by the simple kinetic model.     

Nonstationary Model of a Low-Density Plasma Jet Ejected from a Stationary Plasma Thruster

A time-dependent problem on finding the parameters of a low-density plasma jet ejected from a stationary plasma thruster is analyzed. In contrast to earlier works in which a stationary problem was solved using a Crook-type kinetic model, a set of kinetic equations is derived at the accuracy level accepted in the kinetic theory with allowance for resonant charge-exchange interaction between ions and neutrals. A method to solve the obtained set of equations is developed and used to perform test simulations, some results of which are presented.     

Generating dynamic simulations of movement using computed muscle control

Computation of muscle excitation patterns that produce coordinated movements of muscle-actuated dynamic models is an important and challenging problem. Using dynamic optimization to compute excitation patterns comes at a large computational cost, which has limited the use of muscle-actuated simulations. This paper introduces a new algorithm, which we call computed muscle control, that uses static optimization along with feedforward and feedback controls to drive the kinematic trajectory of a musculoskeletal model toward a set of desired kinematics. We illustrate the algorithm by computing a set of muscle excitations that drive a 30-muscle, 3-degree-of-freedom model of pedaling to track measured pedaling kinematics and forces. Only 10 min of computer time were required to compute muscle excitations that reproduced the measured pedaling dynamics, which is over two orders of magnitude faster than conventional dynamic optimization techniques. Simulated kinematics were within 1 degrees of experimental values, simulated pedal forces were within one standard deviation of measured pedal forces for nearly all of the crank cycle, and computed muscle excitations were similar in timing to measured electromyographic patterns. The speed and accuracy of this new algorithm improves the feasibility of using detailed musculoskeletal models to simulate and analyze movement.     

Cross-bridge model of muscle contraction. Quantitative analysis

We recently presented, in a qualitative manner, a cross-bridge model of muscle contraction which was based on a biochemical kinetic cycle for the actomyosin ATPase activity. This cross-bridge model consisted of two cross-bridge states detached from actin and two cross-bridge states attached to actin. In the present paper, we attempt to fit this model quantitatively to both biochemical and physiological data. We find that the resulting complete cross-bridge model is able to account reasonably well for both the isometric transient data observed when a muscle is subjected to a sudden change in length and for the relationship between the velocity of muscle contraction in vivo and the actomyosin ATPase activity in vitro. This model also illustrates the interrelationship between biochemical and physiological data necessary for the development of a complete cross-bridge model of muscle contraction.     

A kinetic model of muscles: modeling stationary contractions]

Using a recently proposed model of muscle contraction with a modified six-state kinetic scheme of the cross-bridge cycle, computer simulation was made of the dependence of the muscle fibre tension, stiffness and ATPase rate on the contraction velocity and concentrations of the substrate and products of the ATPase reaction. It is shown that the model well describes the experimental data.     

Regulation of oxidative phosphorylation through parallel activation

When the mechanical work intensity in muscle increases, the elevated ATP consumption rate must be matched by the rate of ATP production by oxidative phosphorylation in order to avoid a quick exhaustion of ATP. The traditional mechanism of the regulation of oxidative phosphorylation, namely the negative feedback involving [ADP] and [Pi] as regulatory signals, is not sufficient to account for various kinetic properties of the system in intact skeletal muscle and heart in vivo. Theoretical studies conducted using a dynamic computer model of oxidative phosphorylation developed previously strongly suggest the so-called each-step-activation (or parallel activation) mechanism, due to which all oxidative phosphorylation complexes are directly activated by some cytosolic factor/mechanism related to muscle contraction in parallel with the activation of ATP usage and substrate dehydrogenation by calcium ions. The present polemic article reviews and discusses the growing evidence supporting this mechanism and compares it with alternative mechanisms proposed in the literature. It is concluded that only the each-step-activation mechanism is able to explain the rich set of various experimental results used as a reference for estimating the validity and applicability of particular mechanisms.     

Modeling and simulation of musculoskeletal system of human lower limb based on tensegrity structure

Abstract

In this paper, a mechanical model of the skeletal muscle of human lower limb system is established by using the Hill muscle model and kinetic equation of the movement of lower extremities according to the attachment positions of skeletal muscle. State vector and neural control are delineated by the direct configuration method. Changes of gait and skeletal muscle stress during walking process are analyzed with energy consumption as objective function. Results illustrate that simulation data are in good agreement with actual walking gait data. Feasibility and correctness of the designed model and control behavior of skeletal muscle tension structure are also verified.     

A functionally based model for hydrolysis of cellulose by fungal cellulase

A new functionally based kinetic model for enzymatic hydrolysis of pure cellulose by the Trichoderma cellulase system is presented. The model represents the actions of cellobiohydrolases I, cellobiohydrolase II, and endoglucanase I; and incorporates two measurable and physically interpretable substrate parameters: the degree of polymerization (DP) and the fraction of beta-glucosidic bonds accessible to cellulase, F(a) (Zhang and Lynd, 2004). Initial enzyme-limited reaction rates simulated by the model are consistent with several important behaviors reported in the literature, including the effects of substrate characteristics on exoglucanase and endoglucanase activities; the degree of endo/exoglucanase synergy; the endoglucanase partition coefficient on hydrolysis rates; and enzyme loading on relative reaction rates for different substrates. This is the first cellulase kinetic model involving a single set of kinetic parameters that is successfully applied to a variety of cellulosic substrates, and the first that describes more than one behavior associated with enzymatic hydrolysis. The model has potential utility for data accommodation and design of industrial processes, structuring, testing, and extending understanding of cellulase enzyme systems when experimental date are available, and providing guidance for functional design of cellulase systems at a molecular scale. Opportunities to further refine cellulase kinetic models are discussed, including parameters that would benefit from further study.     

Activation of striated muscle: nearest-neighbor regulatory-unit and cross-bridge influence on myofilament kinetics

We have formulated a three-compartment model of muscle activation that includes both strong cross-bridge (XB) and Ca(2+)-activated regulatory-unit (RU) mediated nearest-neighbor cooperative influences. The model is based on the tight coupling premise--that XB retain activating Ca(2+) on the thin filament. Using global non-linear least-squares, the model produced excellent fits to experimental steady-state force-pCa and ATPase-pCa data from skinned rat soleus fibers. In terms of the model, nearest-neighbor influences over the range of Ca(2+) required for activation cause the Ca(2+) dissociation rate from regulatory-units (k(off)) to decrease and the cross-bridge association rate (f) to increase each more than ten-fold. Moreover, the rate variations occur in separate Ca(2+) regimes. The energy of activation governing f is strongly influenced by both neighboring RU and XB. In contrast, the energy of activation governing k(off) is less affected by neighboring XB than by neighboring RU. Nearest-neighbor cooperative influences provide both an overall sensitization to Ca(2+) and the well-known steep response of force to free Ca(2+). The apparent sensitivity for Ca(2+)-activation of force and ATPase is a function of cross-bridge kinetic rates. The model and derived parameter set produce simulated behavior in qualitative agreement with steady-state experiments reported in the literature for partial TnC replacement, increased [P(i)], increased [ADP], and MalNEt-S1 addition. The model is an initial attempt to construct a general theory of striated muscle activation-one that can be consistently used to interpret data from various types of muscle manipulation experiments.     

Allosteric regulatory properties of muscle phosphofructokinase

We have reviewed the allosteric regulatory properties of skeletal muscle phosphofructokinase and recent results on the phosphorylation of this enzyme. The number and affinities of various ligand binding sites are described, and a simple three state model is presented to explain the kinetic and ligand-binding properties of the enzyme. Data describing a lack of fit to a concerted transition model are presented. The widespread occurrence of partial phosphorylation of phosphofructokinase at a specific site near the carboxyl terminus is documented, as well as the lack of significant kinetic consequences of such phosphorylation.     

Intermediate oxygen exchange catalyzed by the actin-activated skeletal myosin adenosinetriphosphatase

Considerable effort has been devoted to understanding the mechanism of 18O exchange in skinned skeletal and insect muscle fibers. However, a full understanding of the mechanism of 18O exchange in muscle fibers requires an understanding of the mechanism of 18O exchange in the simpler in vitro systems employing myosin subfragment 1 (S-1) and heavy meromyosin (HMM). In the present study, using both S-1 and S-1 covalently cross-linked to actin, we show first that over a wide range of temperature, ionic strength, and actin concentration there is only one pathway of 18O exchange with S-1. This is also the case with HMM except at very low ionic strength and low actin concentration, and even here, the data can be explained if 20% of the HMM is denatured in such a way that it shows no 18O exchange. Our results also show that actin markedly decreases the rate of 18O exchange. If it is assumed that Pi release is rate limiting, the four-state kinetic model of the actomyosin ATPase cannot fit these 18O exchange data. However, if it is assumed that the ATP hydrolysis step is rate limiting and Pi release is very fast, the four-state kinetic model can qualitatively fit these data although the fit is not perfect. A better fit to the 18O exchange data can be obtained with the six-state kinetic model of the actomyosin ATPase, but this fit requires the assumption that, at saturating actin concentration, the rate of Pi rotation is about 9-fold slower than the rate of reversal of the ATP hydrolysis step.     

牛肉中单增李斯特菌的热失活模型

【目的】建立牛肉中单增李斯特菌的热失活动力学模型。【方法】将接种了3种不同血清型的单增李斯特菌混合菌液的牛肉分别在55℃、57.5℃、60℃、63℃、66℃和70℃进行热处理,在不同温度条件下单增李斯特菌数从109CFU/g下降至103CFU/g,其热失活曲线用修正的Gompertz模型进行了拟合;利用线性模型对单增李斯特菌的相对失活率(μ)和所持续时间(M)的自然对数值与温度(55℃-70℃)进行拟合;通过在59℃和64℃对牛肉中单增李斯特菌热处理,对所建的模型进行了验证。【结果】建立了牛肉中单增李斯特菌热失活动力学的一级模型和二级模型,经验证其准确因子和偏差因子均在可接受范围内。【结论】本研究所建立的模型能较好的模拟不同温度(55℃-70℃)对牛肉中单增李斯特菌热失活的影响。     

Combined kinetic mechanism describing activation and inhibition of muscle glycogen phosphorylase b by adenosine 5'-monophosphate

The kinetic analysis of the glycogen chain growth reaction catalyzed by glycogen phosphorylase b from rabbit skeletal muscle has been carried out over a wide range of concentrations of AMP under the saturation of the enzyme by glycogen. The applicability of 23 different variants of the kinetic model involving the interaction of AMP and glucose 1-phosphate binding sites in the dimeric enzyme molecule is considered. A kinetic model has been proposed which assumes: (i) the independent binding of one molecule of glucose 1-phosphate in the catalytic site on the one hand, and AMP in both allosteric effector sites and both nucleoside inhibitor sites of the dimeric enzyme molecule bound by glycogen on the other hand; (ii) the binding of AMP in one of the allosteric effector sites results in an increase in the affinity of other allosteric effector site to AMP; (iii) the independent binding of AMP to the nucleoside inhibitor sites of the dimeric enzyme molecule; (iv) the exclusive binding of the second molecule of glucose 1-phosphate in the catalytic site of glycogen phosphorylase b containing two molecules of AMP occupying both allosteric effector sites; and (v) the catalytic act occurs exclusively in the complex of the enzyme with glycogen, two molecules of AMP occupying both allosteric effector sites, and two molecules of glucose 1-phosphate occupying both catalytic sites.     

A musculoskeletal model of the hand and wrist: model definition and evaluation

Abstract

To improve our understanding on the neuromechanics of finger movements, a comprehensive musculoskeletal model is needed. The aim of this study was to build a musculoskeletal model of the hand and wrist, based on one consistent data set of the relevant anatomical parameters. We built and tested a model including the hand and wrist segments, as well as the muscles of the forearm and hand in OpenSim. In total, the model comprises 19 segments (with the carpal bones modeled as one segment) with 23 degrees of freedom and 43 muscles. All required anatomical input data, including bone masses and inertias, joint axis positions and orientations as well as muscle morphological parameters (i.e. PCSA, mass, optimal fiber length and tendon length) were obtained from one cadaver of which the data set was recently published. Model validity was investigated by first comparing computed muscle moment arms at the index finger metacarpophalangeal (MCP) joint and wrist joint to published reference values. Secondly, the muscle forces during pinching were computed using static optimization and compared to previously measured intraoperative reference values. Computed and measured moment arms of muscles at both index MCP and wrist showed high correlation coefficients (r?=?0.88 averaged across all muscles) and modest root mean square deviation (RMSD?=?23% averaged across all muscles). Computed extrinsic flexor forces of the index finger during index pinch task were within one standard deviation of previously measured in-vivo tendon forces. These results provide an indication of model validity for use in estimating muscle forces during static tasks.