Filament Theory Of Contraction Research Articles

Implementing Guided Inquiry Active Learning in an Online Synchronous Classroom and its Impact on Test Question Performance

Guided inquiry is an active learning technique featuring collaborative group learning with a structured set of models and highly structured questions for students to discuss and answer. Moving this technique to an online delivery format presents challenges, leading to questions about the effectiveness of this technique during online instruction. This study looked at the synchronous online delivery of a sliding filament theory guided inquiry activity (Brown 2015) and scores on related exam questions in anatomy classes at Salt Lake Community College. Students who participated in the guided inquiry activity had a median score of 79% on questions related to the sliding filament theory of muscle contraction while those that did not participate in guided inquiry had a median score of 61%, revealing a medium effect on student test scores. This suggests that the guided inquiry activity was successful at improving student understanding and retention when delivered in the online teaching environment.

Physiological Mechanisms of Eccentric Contraction and Its Applications: A Role for the Giant Titin Protein.

When active muscles are stretched, our understanding of muscle function is stretched as well. Our understanding of the molecular mechanisms of concentric contraction has advanced considerably since the advent of the sliding filament theory, whereas mechanisms for increased force production during eccentric contraction are only now becoming clearer. Eccentric contractions play an important role in everyday human movements, including mobility, stability, and muscle strength. Shortly after the sliding filament theory of muscle contraction was introduced, there was a reluctant recognition that muscle behaved as if it contained an “elastic” filament. Jean Hanson and Hugh Huxley referred to this structure as the “S-filament,” though their concept gained little traction. This additional filament, the giant titin protein, was identified several decades later, and its roles in muscle contraction are still being discovered. Recent research has demonstrated that, like activation of thin filaments by calcium, titin is also activated in muscle sarcomeres by mechanisms only now being elucidated. The mdm mutation in mice appears to prevent activation of titin, and is a promising model system for investigating mechanisms of titin activation. Titin stiffness appears to increase with muscle force production, providing a mechanism that explains two fundamental properties of eccentric contractions: their high force and low energetic cost. The high force and low energy cost of eccentric contractions makes them particularly well suited for athletic training and rehabilitation. Eccentric exercise is commonly prescribed for treatment of a variety of conditions including sarcopenia, osteoporosis, and tendinosis. Use of eccentric exercise in rehabilitation and athletic training has exploded to include treatment for the elderly, as well as muscle and bone density maintenance for astronauts during long-term space travel. For exercise intolerance and many types of sports injuries, experimental evidence suggests that interventions involving eccentric exercise are demonstrably superior to conventional concentric interventions. Future work promises to advance our understanding of the molecular mechanisms that confer high force and low energy cost to eccentric contraction, as well as signaling mechanisms responsible for the beneficial effects of eccentric exercise in athletic training and rehabilitation.

New hypothesis for mechanism of sliding filament theory of skeletal muscle contraction

Background: Current understanding of skeletal muscle contraction is based on the sliding filament theory proposed independently by A.F. Huxley and H.E. Huxley (1954). The sliding filament theory very well explained shortening of skeletal muscle during contraction with reference to a single sarcomere with movement of Z discs toward center of that particular sarcomere. However, when we consider shortening of multiple sarcomeres in a myofibril arranged in series, the sliding filament theory fails to justify the movement of Z discs as each Z disc is being pulled in opposite direction by myosin heads of adjacent sarcomeres. Aims & Objectives: To find out alternate possible mechanism of Z disc movement on either side of A band if movement toward center by both sides is not possible. Materials and Methods: We have prepared a simulating model of sliding filament theory and observed mechanism of contraction on it. Results: The sliding filament theory fails to explain the movement of Z discs when all sarcomeres in a myofibril are contracting simultaneously. Therefore, we proposed a new hypothesis that Z discs and actin filaments in the half part of each sarcomere, which is toward origin end of muscle fiber, are not pulled toward center of myosin filament instead myosin filament slide toward origin end, and in the other half of each sarcomere (which is toward insertion end) actin filaments slide over myosin filament toward origin end of the muscle. Conclusion: This study adds a new insight into the sliding filament theory of muscle contraction and needs further confirmation on electron microscopic studies.

An Active Role for Titin in Skeletal Muscle

The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate active force. Recent studies have observed enhanced titin-based force in activated rabbit psoas myofibrils that were stretched to lengths which exceed filament overlap. These forces cannot be accounted for in the current theory, thus, alternative mechanisms of force production should be considered. Titin has been speculated to play a role in active force by binding to the thin filament, shortening and stiffening its spring length during skeletal muscle activation. To further investigate this, the present study uses a model (mdm) in which the titin protein is mutated. This study aims to test the hypothesis that the region of titin that binds to the thin filament during activation is contained within the mdm deletion in titin. If the deleted region of mdm titin modulates titin-based stiffness via activation-dependent binding to the thin filament, mdm would be deficient in this binding, resulting in a more compliant titin spring. To test this hypothesis, mouse psoas myofibrils were passively and actively stretched to ∼6.0 μm/sarcomere. When wild-type myofibrils were actively stretched to average sarcomere lengths that exceed filament overlap, force continued to increase and remained greater than the passive force at all lengths. This trend was not observed in mdm myofibrils. Actively stretched mdm myofibrils were more compliant than wild-type myofibrils and did not differ from passive wild-type or mdm myofibrils. An enhanced state of titin-based force has now been demonstrated in rabbit and mouse myofibrils, suggesting that modulation of titin force during activation may be an inherent property of skeletal muscle. This property is disrupted in mdm, suggesting that a critical function in the enhancement of titin-based force is lost in mdm titin.

Titin force is enhanced in actively stretched skeletal muscle.

The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate force during activation. Within the constraints of this theory, isometric, steady-state force produced during muscle activation is proportional to the amount of filament overlap. Previous studies from our laboratory demonstrated enhanced titin-based force in myofibrils that were actively stretched to lengths which exceeded filament overlap. This observation cannot be explained by the sliding filament theory. The aim of the present study was to further investigate the enhanced state of titin during active stretch. Specifically, we confirm that this enhanced state of force is observed in a mouse model and quantify the contribution of calcium to this force. Titin-based force was increased by up to four times that of passive force during active stretch of isolated myofibrils. Enhanced titin-based force has now been demonstrated in two distinct animal models, suggesting that modulation of titin-based force during active stretch is an inherent property of skeletal muscle. Our results also demonstrated that 15% of the enhanced state of titin can be attributed to direct calcium effects on the protein, presumably a stiffening of the protein upon calcium binding to the E-rich region of the PEVK segment and selected Ig domain segments. We suggest that the remaining unexplained 85% of this extra force results from titin binding to the thin filament. With this enhanced force confirmed in the mouse model, future studies will aim to elucidate the proposed titin-thin filament interaction in actively stretched sarcomeres.

Motors or dynamics: What really moves chromosomes?

Motors or dynamics: What really moves chromosomes?

Body size and the neural control of movement

Summary Nervous systems, muscles, and motor organs (biomechanics) generate movement cooperatively and should therefore change coordinately as body size changes. Proving this hypothesis requires a description of the nervous system, muscle, and biomechanics of individual species and comparison of these properties across a collection of species spanning a large size range. Obtaining these data in even one species is daunting, and we are far from reaching a general theory of how nervous system, muscle, and biomechanics depend on body size. Sufficient cross-species data nonetheless exist to identify some consequences of body size on the neural control of movement, which form the focus of this Primer: for example, locomotor cycle period depends on leg length; large animals should devote more neural resources to hazard avoidance and stride correction; the importance of gravity and momentum increases, and of passive muscle properties decreases, with limb size; and the medium in which movements occur affects these size dependencies. These considerations suggest that, in applying biological data to robotic design, proper ‘size' should be maintained across all levels (i.e., if small-animal neural mechanisms are used, so should small-animal muscle and biomechanical properties).

Highlights from the Literature

Highlights from the Literature

Structural mechanisms in muscle. Jean Hanson’s legacy: to celebrate the 50th anniversary of the sliding filament theory of muscle contraction

Structural mechanisms in muscle. Jean Hanson’s legacy: to celebrate the 50th anniversary of the sliding filament theory of muscle contraction

Perturbed Equilibria of Myosin Binding in Airway Smooth Muscle: Bond-Length Distributions, Mechanics, and ATP Metabolism

We carried out a detailed mathematical analysis of the effects of length fluctuations on the dynamically evolving cross-bridge distributions, simulating those that occur in airway smooth muscle during breathing. We used the latch regulation scheme of Hai and Murphy ( Am. J. Physiol. Cell Physiol. 255:C86–C94, 1988) integrated with Huxley’s sliding filament theory of muscle contraction. This analysis showed that imposed length fluctuations decrease the mean number of attached bridges, depress muscle force and stiffness, and increase force-length hysteresis. At frequencies >0.1 Hz, the bond-length distribution of slowly cycling latch bridges changed little over the stretch cycle and contributed almost elastically to muscle force, but the rapidly cycling cross-bridge distribution changed substantially and dominated the hysteresis. By contrast, at frequencies <0.033 Hz this behavior was reversed: the rapid cycling cross-bridge distribution changed little, effectively functioning as a constant force generator, while the latch bridge bond distribution changed substantially and dominated the stiffness and hysteresis. The analysis showed the dissociation of force/length hysteresis and cross-bridge cycling rates when strain amplitude exceeds 3%; that is, there is only a weak coupling between net external mechanical work and the ATP consumption required for cycling cross-bridges during the oscillatory steady state. Although these results are specific to airway smooth muscle, the approach generalizes to other smooth muscles subjected to cyclic length fluctuations.

Ultrastructural patterns of ferritin permeation into glutaraldehyde‐fixed freeze‐fractured sarcomeres characterize stages of contraction in striated muscle

AbstractWe show that “fracture—permeation”—a method developed to assess the compactness of the cytoplasm—can establish the distribution of intermolecular spaces in the sarcomeres of glutaraldehyde‐fixed striated muscle. As examples of striated muscle, we use sartorius muscle from toad (Bufo marinus) and papillary cardiac muscle from the left ventricle of Sprague—Dawley rats. Tissues were fixed in glutaraldehyde, frozen, cross‐fractured in liquid nitrogen, and thawed. Tissue fragments were immersed in concentrated solutions of native ferritin (30% w/v). Random fractures gave ferritin direct access to all regions of the sarcomere. We show that a sequence of four qualitatively distinct patterns of ferritin distribution is associated to a progressive sequence of sarcomere lengths. The correspondence between sarcomere lengths and patterns of ferritin permeation permits the recognition of sarcomeres in rigor (no penetration of ferritin), stretched (penetration into the I band and H zone), or at rest length (penetration restricted to the I band). Similar patterns of ferritin permeation can also be recognized in oblique sections. In cardiac muscle, ferritin permeates into the A bands of contracted sarcomeres and shows an increase in disorder within the filament lattice during contraction. The patterns of ferritin permeation observed in sarcomeres in rigor, stretched, or at rest length are those predicted from changes in filament overlapping proposed by Huxley's “sliding filament theory of muscle contraction.” Our results illustrate the power of fracture‐permeation to investigate intermolecular distances in cytoplasmic matrices.

An explanation of the relationships between mass, metabolic rate and characteristic skeletal length for birds and mammals

A theory explaining the relationships between metabolic rate and body mass for birds and mammals is developed in terms of the mitochondrion theory of aerobic metabolism, the sliding filament theory of muscle contraction, simple models of vertebrate anatomy and activity, and other propositions. Both body mass and metabolic rates are shown to result from a homogeneous vertebrate design quantitatively expressed in terms of a set of nearly invariant parameters with five degrees of freedom: propulsion technique, mitochondrion capability, non-skeletal muscle mass exponent, characteristic skeletal length, and sturdiness factor. The first three of the degrees of freedom are phylogenetic group specific. The last two vary considerably even within a single species. The theory is shown to agree satisfactorily with placental mammal, marsupial mammal, passerine bird and nonpasserine bird data. Algorithms for determining metabolic rates and body mass as functions of skeletal characteristic length are developed and quantitative estimates of the constants occurring in the algorithms are given.

The measurement and dynamic implications of thin filament lengths in heart muscle.

1. The lengths of the thin filaments in amphibian and mammalian cardiac muscle have been determined from electron micrographs of serial transverse sections. Thin filament lengths in frog atrial trabeculae range from 0.8 to greater than 1.3 micrometers, with a maximum possible error of 0.14--0.15 micrometer. In rat atrial tissue the span is from 0.6 to more than 1.1 micrometer, whereas in rat papillary muscle the breadth of the distribution is much narrower, from 0.9 to greater than 1.1 micrometer. Double overlap of thin filaments should, therefore, exist over a wide range of sarcomere lenghts. Thin filaments from opposite halves of a sarcomere accommodate each other by flexing up to an angle of about 2 degrees and moving from the trigonal position among the thick filaments to the centre of the region between two thick filaments. Such rearrangement probably contributes to the internal resistance to shortening in the muscle. 2. Except for the variation in thin filament lengths, the over-all morphology of the cardiac sarcomere is generally similar to that found in skeletal muscle. Thick filaments in heart muscle are uniform in length, and their profiles change along their lengths. They are generally round in the M band, triangular adjacent to the M band, round again in the overlap region, and either round or triangular near the tapered tips. The M bridges in rat cardiac tissue link neighbouring thick filaments to form a symmetric hexagonal array, whereas in the frog atrium, the M bridge connexions are incomplete and often form isolated triangular clusters. 3. Computed sarcomere length-developed tension curves were calculated using the thin filament length distributions and the assumptions basic to the sliding filament theory of muscle contraction. The curves for atrial tissue have plateau regions approximately as wide as the one-half micron variation in thin filament length. 4. Work done against the internal loads during systole may be stored as potential energy and released during diastole to produce sarcomeric re-extension.

Myosin aggregates as a requirement for contraction and a proposal to the mechanism of contraction of actomyosin systems.

Glycerinated fibers of rabbit psoas muscle showed no augmentation of tension development upon incubation with heavy meromyosin, irrespective of whether the fibers were of standard length, stretched, or extracted of their myosin content. The effect of heavy meromyosin was to suppress contraction. These observations are in disagreement with certain recent published reports (Oplatka et al., 1974) and do tend to support the current sliding filament theory of muscle contraction and the necessity of bipolar myosin filaments for contraction. A possible mechanism of contraction in protein systems, including tension generation in actomyosin fibers and superprecipitation, is described emphasizing the polarity of both myosin and actin filaments.

Isotonic lengthening and shortening movements of cat soleus muscle.

1. By supplying pulses to different subdivisions of the ventral nerve roots in rotation it was possible to obtain smooth contractions of cat soleus with low rates of stimulation.2. After contracting isometrically the muscle was subjected to ;step' changes in tension after which it lengthened or shortened isotonically.3. Isotonic lengthening movements usually began relatively slowly but proceeded with increasing velocity; this acceleration was most conspicuous when low rates of stimulation were used.4. At low rates of stimulation the isotonic lengthening movement often continued beyond the length at which the muscle could have generated that tension in an isometric contraction. The muscle then shortened slowly back toward that length.5. Isotonic shortening movements began relatively rapidly, but as shortening continued the movement became slower, and often had an irregular oscillatory course.6. The isotonic movements are discussed in relation to the sliding filament theory of muscle contraction.7. The compliance of the series elastic elements was calculated from the relative amplitudes of the ;step' changes in tension and length. The stiffness of this component increased with increasing muscle tension.

The mechanical properties of cat soleus muscle during controlled lengthening and shortening movements.

1. By supplying pulses to different subdivisions of the ventral nerve roots in rotation, it was possible to obtain smooth contractions of cat soleus with low rates of stimulation.2. After contracting isometrically the muscle was subjected to constant velocity lengthening or shortening movements.3. During shortening the tension always fell below the isometric value. The fall in tension was usually greatest when low rates of stimulation were used.4. The effect of lengthening on tension depended on the rate of stimulation. At high rates of stimulation the tension during lengthening always rose above the isometric tension. At lower rates of stimulation (5-15 pulses/sec) the tension rose at the beginning of an extension, but decreased later in the movement to a level that was often less than the isometric tension corresponding to that muscle length. At these stimulus rates the tension during isometric contraction was usually higher than during a sustained movement in either direction.5. At low rates of stimulation longitudinal vibratory movements of more than 0.1 mm also reduced the tension far below the isometric value, whereas the reduction was quite slight when the rate of stimulation was high.6. The isometric tension during smooth contractions at low stimulus rates was remarkable in the following respects: it developed rather slowly, it was higher than the tension during or immediately after movements, and it was only slowly regained after movement had ceased.7. The results are discussed in relation to the sliding filament theory of muscle contraction, which, with certain assumptions, provides an explanation for many of the findings.