scholarly journals Hypothesis: Single Actomyosin Properties Account for Ensemble Behavior in Active Muscle Shortening and Isometric Contraction

2020 ◽  
Vol 21 (21) ◽  
pp. 8399
Author(s):  
Alf Månsson

Muscle contraction results from cyclic interactions between myosin II motors and actin with two sets of proteins organized in overlapping thick and thin filaments, respectively, in a nearly crystalline lattice in a muscle sarcomere. However, a sarcomere contains a huge number of other proteins, some with important roles in muscle contraction. In particular, these include thin filament proteins, troponin and tropomyosin; thick filament proteins, myosin binding protein C; and the elastic protein, titin, that connects the thin and thick filaments. Furthermore, the order and 3D organization of the myofilament lattice may be important per se for contractile function. It is possible to model muscle contraction based on actin and myosin alone with properties derived in studies using single molecules and biochemical solution kinetics. It is also possible to reproduce several features of muscle contraction in experiments using only isolated actin and myosin, arguing against the importance of order and accessory proteins. Therefore, in this paper, it is hypothesized that “single molecule actomyosin properties account for the contractile properties of a half sarcomere during shortening and isometric contraction at almost saturating Ca concentrations”. In this paper, existing evidence for and against this hypothesis is reviewed and new modeling results to support the arguments are presented. Finally, further experimental tests are proposed, which if they corroborate, at least approximately, the hypothesis, should significantly benefit future effective analysis of a range of experimental studies, as well as drug discovery efforts.

2000 ◽  
Vol 6 (S2) ◽  
pp. 76-77
Author(s):  
Rhea J.C. Levine ◽  
Irina Kulakovskaya ◽  
H. Lee Sweeney ◽  
Saul Winegrad ◽  
Zhaohui Yang

In mammalian skeletal and cardiac muscles, regulation of activity occurs when calcium binds to troponin on thin filaments, which ultimately results in exposure of myosin-binding sites on actin. However, modulation of contractile function, affecting such parameters as calcium sensitivity, the rate of rise of tension, the expression of maximum tension and/or the rate of onset of relaxation, is also calcium dependent. It is, in part, a property of the thick filament itself and its component myosin and/or accessory proteins. Among these are phosphorylation of myosin regulatory light chains or light chain 2 (RLCs; LC2) and in cardiac, but not skeletal fibers, phosphorylation of myosin-binding protein C (MyBP-C).Gentle methods of separating thick filaments from small tissue specimens, subjected to various experimental protocols designed to explore the functional parameters of such modulatory activities, allow examination of any accompanying structural changes.


2011 ◽  
Vol 279 (1730) ◽  
pp. 981-990 ◽  
Author(s):  
Kiisa C. Nishikawa ◽  
Jenna A. Monroy ◽  
Theodore E. Uyeno ◽  
Sang Hoon Yeo ◽  
Dinesh K. Pai ◽  
...  

Recent studies have demonstrated a role for the elastic protein titin in active muscle, but the mechanisms by which titin plays this role remain to be elucidated. In active muscle, Ca 2+ -binding has been shown to increase titin stiffness, but the observed increase is too small to explain the increased stiffness of parallel elastic elements upon muscle activation. We propose a ‘winding filament’ mechanism for titin's role in active muscle. First, we hypothesize that Ca 2+ -dependent binding of titin's N2A region to thin filaments increases titin stiffness by preventing low-force straightening of proximal immunoglobulin domains that occurs during passive stretch. This mechanism explains the difference in length dependence of force between skeletal myofibrils and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as motors that pull thin filaments towards the M-line, but also as rotors that wind titin on the thin filaments, storing elastic potential energy in PEVK during force development and active stretch. Energy stored during force development can be recovered during active shortening. The winding filament hypothesis accounts for force enhancement during stretch and force depression during shortening, and provides testable predictions that will encourage new directions for research on mechanisms of muscle contraction.


Author(s):  
H. Mohri

In 1959, Afzelius observed the presence of two rows of arms projecting from each outer doublet microtubule of the so-called 9 + 2 pattern of cilia and flagella, and suggested a possibility that the outer doublet microtubules slide with respect to each other with the aid of these arms during ciliary and flagellar movement. The identification of the arms as an ATPase, dynein, by Gibbons (1963)strengthened this hypothesis, since the ATPase-bearing heads of myosin molecules projecting from the thick filaments pull the thin filaments by cross-bridge formation during muscle contraction. The first experimental evidence for the sliding mechanism in cilia and flagella was obtained by examining the tip patterns of molluscan gill cilia by Satir (1965) who observed constant length of the microtubules during ciliary bending. Further evidence for the sliding-tubule mechanism was given by Summers and Gibbons (1971), using trypsin-treated axonemal fragments of sea urchin spermatozoa. Upon the addition of ATP, the outer doublets telescoped out from these fragments and the total length reached up to seven or more times that of the original fragment. Thus, the arms on a certain doublet microtubule can walk along the adjacent doublet when the doublet microtubules are disconnected by digestion of the interdoublet links which connect them with each other, or the radial spokes which connect them with the central pair-central sheath complex as illustrated in Fig. 1. On the basis of these pioneer works, the sliding-tubule mechanism has been established as one of the basic mechanisms for ciliary and flagellar movement.


2008 ◽  
Vol 59 (5) ◽  
Author(s):  
Mirela Dulama ◽  
Nicoleta Deneanu ◽  
Cristian Dulama ◽  
Margarit Pavelescu

The paper presents the experimental tests concerning the treatment by membrane techniques of radioactive aqueous waste. Solutions, which have been treated by using the bench-scale installation, were radioactive simulated secondary wastes from the decontamination process with modified POD. Generally, an increasing of the retention is observed for most of the contaminants in the reverse osmosis experiments with pre-treatment steps. The main reason for taking a chemical treatment approach was to selectively remove soluble contaminants from the waste. In the optimization part of the precipitation step, several precipitation processes were compared. Based on this comparison, mixed [Fe(CN)6]4-/Al3+/Fe2+ was selected as a precipitation process applicable for precipitation of radionuclides and flocculation of suspended solid. Increased efficiencies for cesium radionuclides removal were obtained in natural zeolite adsorption pre-treatment stages and this was due to the fact that volcanic tuff used has a special affinity for this element. Usually, the addition of powdered active charcoal serves as an advanced purifying method used to remove organic compounds and residual radionuclides; thus by analyzing the experimental data (for POD wastes) one can observe a decreasing of about 50% for cobalt isotopes subsequently to the active charcoal adsorption.. The semipermeable membranes were used, which were prepared by the researchers from the Research Center for Macromolecular Materials and Membranes, Bucharest. The process efficiency was monitored by gamma spectrometry.


Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 626
Author(s):  
Riccardo Scazzosi ◽  
Marco Giglio ◽  
Andrea Manes

In the case of protection of transportation systems, the optimization of the shield is of practical interest to reduce the weight of such components and thus increase the payload or reduce the fuel consumption. As far as metal shields are concerned, some investigations based on numerical simulations showed that a multi-layered configuration made of layers of different metals could be a promising solution to reduce the weight of the shield. However, only a few experimental studies on this subject are available. The aim of this study is therefore to discuss whether or not a monolithic shield can be substituted by a double-layered configuration manufactured from two different metals and if such a configuration can guarantee the same perforation resistance at a lower weight. In order to answer this question, the performance of a ballistic shield constituted of a layer of high-strength steel and a layer of an aluminum alloy impacted by an armor piercing projectile was investigated in experimental tests. Furthermore, an axisymmetric finite element model was developed. The effect of the strain rate hardening parameter C and the thermal softening parameter m of the Johnson–Cook constitutive model was investigated. The numerical model was used to understand the perforation process and the energy dissipation mechanism inside the target. It was found that if the high-strength steel plate is used as a front layer, the specific ballistic energy increases by 54% with respect to the monolithic high-strength steel plate. On the other hand, the specific ballistic energy decreases if the aluminum plate is used as the front layer.


2021 ◽  
Vol 11 (11) ◽  
pp. 5008
Author(s):  
Juan José del Coz-Díaz ◽  
Felipe Pedro Álvarez-Rabanal ◽  
Mar Alonso-Martínez ◽  
Juan Enrique Martínez-Martínez

The thermal inertia properties of construction elements have gained a great deal of importance in building design over the last few years. Many investigations have shown that this is the key factor to improve energy efficiency and obtain optimal comfort conditions in buildings. However, experimental tests are expensive and time consuming and the development of new products requires shorter analysis times. In this sense, the goal of this research is to analyze the thermal behavior of a wall made up of lightweight concrete blocks covered with layers of insulating materials in steady- and transient-state conditions. For this, numerical and experimental studies were done, taking outdoor temperature and relative humidity as a function of time into account. Furthermore, multi-criteria optimization based on the design of the experimental methodology is used to minimize errors in thermal material properties and to understand the main parameters that influence the numerical simulation of thermal inertia. Numerical Finite Element Models (FEM) will take conduction, convection and radiation phenomena in the recesses of lightweight concrete blocks into account, as well as the film conditions established in the UNE-EN ISO 6946 standard. Finally, the numerical ISO-13786 standard and the experimental results are compared in terms of wall thermal transmittance, thermal flux, and temperature evolution, as well as the dynamic thermal inertia parameters, showing a good agreement in some cases, allowing builders, architects, and engineers to develop new construction elements in a short time with the new proposed methodology.


1998 ◽  
Vol 78 (2) ◽  
pp. 359-391 ◽  
Author(s):  
BARRY M. MILLMAN

Millman, Barry M. The Filament Lattice of Striated Muscle. Physiol. Rev. 78: 359–391, 1998. — The filament lattice of striated muscle is an overlapping hexagonal array of thick and thin filaments within which muscle contraction takes place. Its structure can be studied by electron microscopy or X-ray diffraction. With the latter technique, structural changes can be monitored during contraction and other physiological conditions. The lattice of intact muscle fibers can change size through osmotic swelling or shrinking or by changing the sarcomere length of the muscle. Similarly, muscle fibers that have been chemically or mechanically skinned can be compressed with bathing solutions containing very large inert polymeric molecules. The effects of lattice change on muscle contraction in vertebrate skeletal and cardiac muscle and in invertebrate striated muscle are reviewed. The force developed, the speed of shortening, and stiffness are compared with structural changes occurring within the lattice. Radial forces between the filaments in the lattice, which can include electrostatic, Van der Waals, entropic, structural, and cross bridge, are assessed for their contributions to lattice stability and to the contraction process.


2015 ◽  
Vol 39 (3) ◽  
pp. 593-603
Author(s):  
Xinghui Zhang ◽  
Jianshe Kang ◽  
Hongzhi Teng ◽  
Jianmin Zhao

Gear and bearing faults are the main causes of gearbox failure. Till now, incipient fault diagnosis of these two components has been a problem and needs further research. In this context, it is found that Lucy–Richardson deconvolution (LRD) proved to be an excellent tool to enhance fault diagnosis in rolling element bearings and gears. LRD’s good identification capabilities of fault frequencies are presented which outperform envelope analysis. This is very critical for early fault diagnosis. The case studies were carried out to evaluate the effectiveness of the proposed method. The results of simulated and experimental studies show that LRD is efficient in alleviating the negative effect of noise and transmission path. The results of simulation and experimental tests demonstrated outperformance of LRD compared to classical envelope analysis for fault diagnosis in rolling element bearings and gears, especially when it is applied to the processing of signals with strong background noise.


2019 ◽  
Vol 126 (1) ◽  
pp. 170-182 ◽  
Author(s):  
Hiroaki Eshima ◽  
Yoshifumi Tamura ◽  
Saori Kakehi ◽  
Kyoko Nakamura ◽  
Nagomi Kurebayashi ◽  
...  

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca2+ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca2+ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca2+ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca2+ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca2+ levels, and Ca2+ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca2+ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca2+ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca2+ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.


2018 ◽  
Vol 42 (4) ◽  
pp. 672-684 ◽  
Author(s):  
Jack A. Rall

One of the most iconic images in biology is the cross-striated appearance of a skeletal muscle fiber. The repeating band pattern shows that all of the sarcomeres are the same length. All of the A bands are the same length and are located in the middle of the sarcomeres. Furthermore, all of the myofibrils are transversely aligned across the muscle fiber. It has been known for 300 yr that skeletal muscle is striated, but only in the last 40 yr has a molecular understanding of the striations emerged. In the 1950s it was discovered that the extraction of myosin from myofibrils abolished the A bands, and the myofibrils were no longer striated. With the further extraction of actin, only the Z disks remained. Strangely, the sarcomere length did not change, and these “ghost” myofibrils still exhibited elastic behavior. The breakthrough came in the 1970s with the discovery of the gigantic protein titin. Titin, an elastic protein ~1 µm in length, runs from the Z disk to the middle of the A band and ensures that each sarcomere is the same length. Titin anchors the A band in the middle of the sarcomere and may determine thick-filament length and thus A-band length. In the 1970s it was proposed that the intermediate filament desmin, which surrounds the Z disks, connects adjacent myofibrils, resulting in the striated appearance of a skeletal muscle fiber.


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