Sarcomere level mechanics of the fast skeletal muscle of the medaka fish larva.

The medaka fish (Oryzias latipes) is a vertebrate model used in developmental biology and genetics. Here we explore its suitability as a model for investigating the molecular mechanisms of human myopathies caused by mutations in sarcomeric proteins. To this end, the relevant mechanical parameters of the intact skeletal muscle of wild-type medaka are determined using the transparent tail at larval stage 40. Tails were mounted at sarcomere length of 2.1 µm in a thermoregulated trough containing physiological solution. Tetanic contractions were elicited at physiological temperature (10°C-30°C) by electrical stimulation, and sarcomere length changes were recorded with nanometer-microsecond resolution during both isometric and isotonic contractions with a striation follower. The force output has been normalized for the actual fraction of the cross section of the tail occupied by the myofilament lattice, as established with transmission electron microscopy (TEM), and then for the actual density of myofilaments, as established with X-ray diffraction. Under these conditions, the mechanical performance of the contracting muscle of the wild-type larva can be defined at the level of the half-thick filament, where ∼300 myosin motors work in parallel as a collective motor, allowing a detailed comparison with the established performance of the skeletal muscle of different vertebrates. The results of this study point out that the medaka fish larva is a suitable model for the investigation of the genotype/phenotype correlations and therapeutic possibilities in skeletal muscle diseases caused by mutations in sarcomeric proteins.NEW & NOTEWORTHY The suitability of the medaka fish as a model for investigating the molecular mechanisms of human myopathies caused by mutations of sarcomeric proteins is tested by combining structural analysis and sarcomere-level mechanics of the skeletal muscle of the tail of medaka larva. The mechanical performance of the medaka muscle, scaled at the level of the myosin-containing thick filament, together with its reduced genome duplication makes this model unique for investigations of the genotype/phenotype correlations in human myopathies.

Residual force depression is not related to positive muscle fascicle work during submaximal voluntary dorsiflexion contractions in humans.

Residual force depression (rFD) following active muscle shortening is assumed to correlate most strongly with muscle work, but this has not been tested during voluntary contractions in humans. Using dynamometry, we compared steady-state ankle joint torques (N = 16) following tibialis anterior (TA) muscle-tendon unit (MTU) lengthening and shortening to the time-matched torque during submaximal voluntary fixed-end dorsiflexion reference contractions (REF) at a matched MTU length and EMG amplitude. Ultrasound revealed significantly reduced (P < 0.001) TA fascicle shortening amplitudes during MTU lengthening without a preload over small and medium amplitudes, respectively, relative to REF. MTU lengthening with a preload over a large amplitude significantly (P < 0.001) increased fascicle shortening relative to REF, as well as stretch amplitudes relative to MTU lengthening without a preload (P = 0.001). Significant (P = 0.028) steady-state fascicle force enhancement relative to REF was observed following MTU lengthening, and was similar among MTU lengthening-hold conditions (3-5%). MTU shortening with and without a preload over small and large amplitudes significantly (P < 0.001) increased positive fascicle and MTU work relative to REF, but significant (P = 0.006) rFD was observed following MTU shortening with a preload (7-10%) only. rFD was linearly related to positive MTU work [rrm (47) = 0.48, P < 0.001], but not positive fascicle work [rrm (47) = 0.16, P = 0.277]. Our findings indicate that MTU lengthening without substantial fascicle stretch enhances steady-state force output, which might arise from less shortening-induced rFD. Our findings also indicate similar rFD following different amounts of positive fascicle/MTU work, which cautions against using work to predict rFD during submaximal voluntary contractions. KEY POINTS: Accurately predicting muscle force is challenging because active muscle shortening depresses force output. The residual force depression (rFD) that exists following active muscle shortening is commonly assumed to correlate strongly and positively with muscle work. We found that tibialis anterior muscle fascicle work and muscle-tendon unit work did not accurately predict rFD during submaximal voluntary dorsiflexion contractions. Fascicle shortening during fixed-end reference contractions also potentially induced rFD of 3-5%, which was similar to the rFD following muscle-tendon unit shortening without a preload. A higher number of active muscle fibres during shortening probably increased rFD, which suggests that motor unit recruitment during shortening might predict rFD.

Conserved mammalian muscle mechanics during eccentric contractions.

Skeletal muscle has a broad range of biomechanical functions, including power generation and energy absorption. These roles are underpinned by the force-velocity relationship, which comprises two distinct components: a concentric and an eccentric force-velocity relationship. The concentric component has been extensively studied across a wide range of muscles with different muscle properties. However, to date, little progress has been made in accurately characterising the eccentric force-velocity relationship in mammalian muscle with varying muscle properties. Consequently, mathematical models of this muscle behaviour are based on a poorly understood phenomenon. Here, we present a comprehensive assessment of the concentric force-velocity and eccentric force-velocity relationships of four mammalian muscles (soleus, extensor digitorum longus, diaphragm and digastric) with varying biomechanical functions, spanning three orders of magnitude in body mass (mouse, rat and rabbits). The force-velocity relationship was characterised using a hyperbolic-linear equation for the concentric component a hyperbolic equation for the eccentric component, at the same time as measuring the rate of force development in the two phases of force development in relation to eccentric lengthening velocity. We demonstrate that, despite differences in the curvature and plateau height of the eccentric force-velocity relationship, the rates of relative force development were consistent for the two phases of the force-time response during isovelocity lengthening ramps, in relation to lengthening velocity, in the four muscles studied. Our data support the hypothesis that this relationship depends on cross-bridge and titin activation. Hill-type musculoskeletal models of the eccentric force-velocity relationship for mammalian muscles should incorporate this biphasic force response. KEY POINTS: The capacity of skeletal muscle to generate mechanical work and absorb energy is underpinned by the force-velocity relationship. Despite identification of the lengthening (eccentric) force-velocity relationship over 80 years ago, no comprehensive study has been undertaken to characterise this relationship in skeletal muscle. We show that the biphasic force response seen during active muscle lengthening is conserved over three orders of magnitude of mammalian skeletal muscle mass. Using mice with a small deletion in titin, we show that part of this biphasic force profile in response to muscle lengthening is reliant on normal titin activation. The rate of force development during muscle stretch may be a more reliable way to describe the forces experienced during eccentric muscle contractions compared to the traditional hyperbolic curve fitting, and functions as a novel predictor of force-velocity characteristics that may be used to better inform hill-type musculoskeletal models and assess pathophysiological remodelling.

The structural and functional effects of myosin regulatory light chain phosphorylation are amplified by increases in sarcomere length and [Ca2+].

Precise regulation of sarcomeric contraction is essential for normal cardiac function. The heart must generate sufficient force to pump blood throughout the body, but either inadequate or excessive force can lead to dysregulation and disease. Myosin regulatory light chain (RLC) is a thick-filament protein that binds to the neck of the myosin heavy chain. Post-translational phosphorylation of RLC (RLC-P) by myosin light chain kinase is known to influence acto-myosin interactions, thereby increasing force production and Ca2+-sensitivity of contraction. Here, we investigated the role of RLC-P on cardiac structure and function as sarcomere length and [Ca2+] were altered. We found that at low, non-activating levels of Ca2+, RLC-P contributed to myosin head disorder, though there were no effects on isometric stress production and viscoelastic stiffness. With increases in sarcomere length and Ca2+-activation, the structural changes due to RLC-P become greater, which translates into greater force production, greater viscoelastic stiffness, slowed myosin detachment rates and altered nucleotide handling. Altogether, these data suggest that RLC-P may alter thick-filament structure by releasing ordered, off-state myosin. These more disordered myosin heads are available to bind actin, which could result in greater force production as Ca2+ levels increase. However, prolonged cross-bridge attachment duration due to slower ADP release could delay relaxation long enough to enable cross-bridge rebinding. Together, this work further elucidates the effects of RLC-P in regulating muscle function, thereby promoting a better understanding of thick-filament regulatory contributions to cardiac function in health and disease. KEY POINTS: Myosin regulatory light chain (RLC) is a thick-filament protein in the cardiac sarcomere that can be phosphorylated (RLC-P), and changes in RLC-P are associated with cardiac dysfunction and disease. This study assesses how RLC-P alters cardiac muscle structure and function at different sarcomere lengths and calcium concentrations. At low, non-activating levels of Ca2+, RLC-P contributed to myofilament disorder, though there were no effects on isometric stress production and viscoelastic stiffness. With increases in sarcomere length and Ca2+-activation, the structural changes due to RLC-P become greater, which translates into greater force production, greater viscoelastic stiffness, slower myosin detachment rate and altered cross-bridge nucleotide handling rates. This work elucidates the role of RLC-P in regulating muscle function and facilitates understanding of thick-filament regulatory protein contributions to cardiac function in health and disease.

Muscle contractile properties directly influence shared synaptic inputs to spinal motor neurons.

Alpha band oscillations in shared synaptic inputs to the alpha motor neuron pool can be considered an involuntary source of noise that hinders precise voluntary force production. This study investigated the impact of changing muscle length on the shared synaptic oscillations to spinal motor neurons, particularly in the physiological tremor band. Fourteen healthy individuals performed low-level dorsiflexion contractions at ankle joint angles of 90° and 130°, while high-density surface electromyography (HDsEMG) was recorded from the tibialis anterior (TA). We decomposed the HDsEMG into motor units spike trains and calculated the motor units' coherence within the delta (1-5 Hz), alpha (5-15 Hz), and beta (15-35 Hz) bands. Additionally, force steadiness and force spectral power within the tremor band were quantified. Results showed no significant differences in force steadiness between 90° and 130°. In contrast, alpha band oscillations in both synaptic inputs and force output decreased as the length of the TA was moved from shorter (90°) to longer (130°), with no changes in delta and beta bands. In a second set of experiments (10 participants), evoked twitches were recorded with the ankle joint at 90° and 130°, revealing longer twitch durations in the longer TA muscle length condition compared to the shorter. These experimental results, supported by a simple computational simulation, suggest that increasing muscle length enhances the muscle's low-pass filtering properties, influencing the oscillations generated by the Ia afferent feedback loop. Therefore, this study provides valuable insights into the interplay between muscle biomechanics and neural oscillations. KEY POINTS: We investigated whether changes in muscle length, achieved by changing joint position, could influence common synaptic oscillations to spinal motor neurons, particularly in the tremor band (5-15 Hz). Our results demonstrate that changing muscle length from shorter to longer induces reductions in the magnitude of alpha band oscillations in common synaptic inputs. Importantly, these reductions were reflected in the oscillations of muscle force output within the alpha band. Longer twitch durations were observed in the longer muscle length condition compared to the shorter, suggesting that increasing muscle length enhances the muscle's low-pass filtering properties. Changes in the peripheral contractile properties of motor units due to changes in muscle length significantly influence the transmission of shared synaptic inputs into muscle force output. These findings prove the interplay between muscle mechanics and neural adaptations.

The effects of muscle starting length on work loop power output of isolated mouse soleus and extensor digitorum longus muscle.

Force-length relationships derived from isometric activations may not directly apply to muscle force production during dynamic contractions. As such, different muscle starting lengths between isometric and dynamic conditions could be required to achieve maximal force and power. Therefore, this study examined the effects of starting length [±5-10% of length corresponding to maximal twitch force (L0)] on work loop (WL) power output (PO), across a range of cycle frequencies, of the soleus (SOL) and extensor digitorum longus muscle (EDL; N=8-10) isolated from ∼8 week old C57 mice. Furthermore, passive work was examined at a fixed cycle frequency to determine the association of passive work and active net work. Starting length affected maximal WL PO of the SOL and EDL across evaluated cycle frequencies (P<0.030, ηp2>0.494). For the SOL, PO produced at -5% L0 was greater than that at most starting lengths (P<0.015, Cohen's d>0.6), except -10% L0 (P=0.135, d<0.4). However, PO produced at -10% L0 versus L0 did not differ (P=0.138, d=0.35-0.49), indicating -5% L0 is optimal for maximal SOL WL PO. For the EDL, WL PO produced at -10% L0 was lower than that at most starting lengths (P<0.032, d>1.08), except versus -5% L0 (P=0.124, d<0.97). PO produced at other starting lengths did not differ (P>0.163, d<1.04). For the SOL, higher passive work was associated with reduced PO (Spearman's r=0.709, P<0.001), but no relationship was observed between passive work and PO of the EDL (Pearson's r=0.191, r2=0.04, P=0.184). This study suggests that starting length should be optimised for both static and dynamic contractions and confirms that the force-length curve during dynamic contractions is muscle specific.

Discipline-specific Torque-Velocity Profiles and Musculotendinous Morphology in Athletes.

OBJECTIVES: The aim of this study was to compare torque-velocity profiles, muscle architecture, tendon dimensions, and bilateral-symmetry between competitive cyclists (CY), competitive runners (RN), ice-hockey players (IH), basketball players (BP), and physically-active individuals (CN) (n=10 for each group). METHODS: Vastus lateralis (VL) muscle and patellar tendon (PT) structures were determined with B-mode ultrasonography, and maximal knee extensor isokinetic torque was assessed at three different velocities. RESULTS: Optimal torque and velocity were lower in runners than CY, BP and IH (p<0.05). Maximal power was similar between the athlete groups but greater than CN (p<0.05). Furthermore, RN and BP reached their peak-torque at longer muscle lengths compared to IH and CY (p<0.05). RN had the lowest VL muscle thickness and the greatest fascicle length, while CY had the greatest pennation angle (p<0.05). CY had the greatest PT thickness, particularly at the proximal and medial sites, while BP at the distal point (p<0.05), with similar trends observed for PT cross-sectional-area. CONCLUSIONS: Our findings show that even if power generating capacity is similar between athletic disciplines, there are discipline-specific muscle adaptations, where particularly runners appear to have muscles adapted for speed rather than torque development, while in cyclists, velocity is sacrificed for torque development.

The role of pennation angle and architectural gearing to rate of force development in dynamic and isometric muscle contractions.

BACKGROUND: Associations between muscle architecture and rate of force development (RFD) have been largely studied during fixed-end (isometric) contractions. Fixed-end contractions may, however, limit muscle shape changes and thus alter the relationship between muscle architecture an RFD. AIM: We compared the correlation between muscle architecture and architectural gearing and knee extensor RFD when assessed during dynamic versus fixed-end contractions. METHODS: Twenty-two recreationally active male runners performed dynamic knee extensions at constant acceleration (2000°s-2) and isometric contractions at a fixed knee joint angle (fixed-end contractions). Torque, RFD, vastus lateralis muscle thickness, and fascicle dynamics were compared during 0-75 and 75-150 ms after contraction onset. RESULTS: Resting fascicle angle was moderately and positively correlated with RFD during fixed-end contractions (r = 0.42 and 0.46 from 0-75 and 75-150 ms, respectively; p < 0.05), while more strongly (p < 0.05) correlated with RFD during dynamic contractions (r = 0.69 and 0.73 at 0-75 and 75-150 ms, respectively; p < 0.05). Resting fascicle angle was (very) strongly correlated with architectural gearing (r = 0.51 and 0.73 at 0-75 ms and 0.50 and 0.70 at 75-150 ms; p < 0.05), with gearing in turn also being moderately to strongly correlated with RFD in both contraction conditions (r = 0.38-0.68). CONCLUSION: Resting fascicle angle was positively correlated with RFD, with a stronger relationship observed in dynamic than isometric contraction conditions. The stronger relationships observed during dynamic muscle actions likely result from different restrictions on the acute changes in muscle shape and architectural gearing imposed by isometric versus dynamic muscle contractions.

Effects of minute oscillation stretching training on muscle and tendon stiffness and walking capability in people with type 2 diabetes.

AIM: we investigated the effects of a 10 week training program (i.e., minute oscillatory stretching; MOS) on the mechanical responses and walking capability in people with type 2 diabetes (T2D). METHODS: seventeen T2D patients performed maximum voluntary contractions of the plantar flexor muscles during which Achilles tendon stiffness (kT) and muscle-tendon stiffness (kM) were evaluated at different percentages of the maximum voluntary force (MVC). In addition, each participant was requested to walk at different walking speeds (i.e. 2, 3, 4, 5, and 6 kmh-1) while their net energy cost of walking (Cnet), cumulative EMG activity per distance travelled (CMAPD) and kinematic parameters (step length, step frequency, the ankle/knee range of motion) were evaluated. RESULTS: maximum tendon elongation increased after MOS training, and kT significantly decreased (between 0 and 20% of MVC). No differences were observed for muscle elongation or kM after training. Cnet decreased after training (at the slowest tested speeds) while no changes in CMAPD were observed. Step length and ankle ROM during walking increased after training at the slowest tested speeds, while step frequency decreased; no significant effects were observed for knee ROM. CONCLUSION: these results indicate the effectiveness of 10 weeks of MOS training in reducing tendon stiffness and the energy cost during walking in people with T2D. This training protocol requires no specific instrumentation, can be easily performed at home, and has a high adherence (92 ± 9%). It could, thus, be useful to mitigate mechanical tendon deterioration and improve physical behaviour in this population.

General Muscle Torque Generator Model for a Two Degree-of-Freedom Shoulder Joint.

Muscle torque generators (MTGs) have been developed as an alternative to muscle-force models, reducing the muscle-force model complexity to a single torque at the joint. Current MTGs can only be applied to single Degree-of-freedom (DoF) joints, leading to complications in modeling joints with multiple-DoFs such as the shoulder. This study aimed to develop an MTG model that accounts for the coupling between 2-DoF at the shoulder joint: shoulder plane of elevation (horizontal abduction/adduction) and shoulder elevation (flexion/extension). Three different 2-DoF MTG equations were developed to model the coupling between these two movements. Net joint torques at the shoulder were determined for 20 participants (10 females and 10 males) in isometric, isokinetic, and passive tests. Curve and surface polynomial fitting were used to find the best general fit for the experimental data in terms of the different degrees of coupling. The models were validated against experimental isokinetic torque data. It was determined that implicit coupling that used interpolation between single-DoF MTGs resulted in the lowest root-mean-square percent error of 8.5%. The work demonstrated that general MTG models can predict torque results that are dependent on multiple-DoFs of the shoulder.

Alignment, cross linking, and beyond: a collagen architect's guide to the skeletal muscle extracellular matrix.

The muscle extracellular matrix (ECM) forms a complex network of collagens, proteoglycans, and other proteins that produce a favorable environment for muscle regeneration, protect the sarcolemma from contraction-induced damage, and provide a pathway for the lateral transmission of contractile force. In each of these functions, the structure and organization of the muscle ECM play an important role. Many aspects of collagen architecture, including collagen alignment, cross linking, and packing density affect the regenerative capacity, passive mechanical properties, and contractile force transmission pathways of skeletal muscle. The balance between fortifying the muscle ECM and maintaining ECM turnover and compliance is highly dependent on the integrated organization, or architecture, of the muscle matrix, especially related to collagen. While muscle ECM remodeling patterns in response to exercise and disease are similar, in that collagen synthesis can increase in both cases, one outcome leads to a stronger muscle and the other leads to fibrosis. In this review, we provide a comprehensive analysis of the architectural features of each layer of muscle ECM: epimysium, perimysium, and endomysium. Further, we detail the importance of muscle ECM architecture to biomechanical function in the context of exercise or fibrosis, including disease, injury, and aging. We describe how collagen architecture is linked to active and passive muscle biomechanics and which architectural features are acutely dynamic and adapt over time. Future studies should investigate the significance of collagen architecture in muscle stiffness, ECM turnover, and lateral force transmission in the context of health and fibrosis.

Effects of pregnancy and lactation on muscle-tendon morphology.

Pregnancy and lactation hormones have been shown to mediate anatomical changes to the musculoskeletal system that generates animal movement. In this study, we characterize changes in the medial gastrocnemius muscle, its tendon and aponeuroses that are likely to have an effect on whole animal movement and energy expenditure, using the rat model system, Rattus norvegicus. We quantified muscle architecture (mass, cross-sectional area, and pennation angle), muscle fiber type and diameter, and Young's modulus of stiffness for the medial gastrocnemius aponeuroses as well as its contribution to Achilles tendon in three groups of three-month-old female rats: virgin, primiparous pregnant, and primiparous lactating animals. We found that muscle mass drops by 23% during lactation but does not change during pregnancy. We also found that during pregnancy muscle fibers switch from Type I to IIa and during lactation from Type IIb to Type I. The stiffness of connective tissues that has a demonstrated role in locomotion, the aponeurosis and tendon, also changed. Pregnant animals had a significantly less stiff aponeurosis. However, tendon stiffness was most affected during lactation, with a significant drop in stiffness and interindividual variation. We propose that the energetic demands of locomotion may have driven the evolution of these anatomical changes in muscle-tendon units during pregnancy and lactation to ensure more energy can be allocated to fetal development and lactation.

The effects of crank power and cadence on muscle fascicle shortening velocity, muscle activation and joint-specific power during cycling.

Whilst people typically choose to locomote in the most economical fashion, during bicycling they will, unusually, chose cadences that are higher than metabolically optimal. Empirical measurements of the intrinsic contractile properties of the vastus lateralis (VL) muscle during submaximal cycling suggest that the cadences that people self-selected might allow for optimal muscle fascicle shortening velocity for the production of knee extensor muscle power. It remains unclear, however, whether this is consistent across different power outputs where the self-selected cadence (SSC) varies. We examined the effect of cadence and external power requirements on muscle neuromechanics and joint power during cycling. VL fascicle shortening velocity, muscle activation and joint-specific power were measured during cycling between 60 and 120 rpm (including SSC), while participants produced 10%, 30% and 50% of peak maximal power. VL shortening velocity increased as cadence increased but was similar across the different power outputs. Although no differences were found in the distribution of joint power across cadence conditions, the absolute knee joint power increased with increasing crank power output. Muscle fascicle shortening velocity increased in VL at the SSC as pedal power demands increased from submaximal towards maximal cycling. A secondary analysis of muscle activation patterns showed minimized activation of VL and other muscles near the SSC at the 10% and 30% power conditions. Minimization of activation with progressively increasing fascicle shortening velocities at the SSC may be consistent with the theory that the optimum shortening velocity for maximizing power increases with the intensity of exercise and recruitment of fast twitch fibers.

Understanding muscle function during perturbed in vivo locomotion using a muscle avatar approach.

The work loop technique has provided key insights into in vivo muscle work and power during steady locomotion. However, for many animals and muscles, ex vivo experiments are not feasible. In addition, purely sinusoidal strain trajectories lack variations in strain rate that result from variable loading during locomotion. Therefore, it is useful to develop an 'avatar' approach in which in vivo strain and activation patterns from one muscle are replicated in ex vivo experiments on a readily available muscle from an established animal model. In the present study, we used mouse extensor digitorum longus (EDL) muscles in ex vivo experiments to investigate in vivo mechanics of the guinea fowl lateral gastrocnemius (LG) muscle during unsteady running on a treadmill with obstacle perturbations. In vivo strain trajectories from strides down from obstacle to treadmill, up from treadmill to obstacle, strides with no obstacle and sinusoidal strain trajectories at the same amplitude and frequency were used as inputs in work loop experiments. As expected, EDL forces produced with in vivo strain trajectories were more similar to in vivo LG forces (R2=0.58-0.94) than were forces produced with the sinusoidal trajectory (average R2=0.045). Given the same stimulation, in vivo strain trajectories produced work loops that showed a shift in function from more positive work during strides up from treadmill to obstacle to less positive work in strides down from obstacle to treadmill. Stimulation, strain trajectory and their interaction had significant effects on all work loop variables, with the interaction having the largest effect on peak force and work per cycle. These results support the theory that muscle is an active material whose viscoelastic properties are tuned by activation, and which produces forces in response to deformations of length associated with time-varying loads.

Muscle function during cross-country skiing at different speed and incline conditions.

The human musculoskeletal system is well adapted to use energy-efficient muscle-tendon mechanics during walking and running, but muscle behaviour during on-snow locomotion is unknown. Here, we examined muscle and muscle-tendon unit behaviour during diagonal-style cross-country roller skiing at three speed and incline conditions to examine whether skiers can exploit energy-saving mechanisms of the muscle-tendon unit. We assessed lower leg muscle and muscle-tendon unit mechanics and muscle activity in 13 high-level skiers during treadmill roller skiing using synchronised ultrasound, motion capture, electromyography and ski-binding force measurements. Participants skied using diagonal style at 2.5 and 3.5 m s-1 up 5 deg, and at 2.5 m s-1 up 10 deg. We found an uncoupling of muscle and joint behaviour during most parts of the propulsive kick phase in all conditions (P<0.01). Gastrocnemius muscle fascicles actively shortened ∼0.9 cm during the kick phase, while the muscle-tendon unit went through a stretch-shortening cycle. Peak muscle-tendon unit shortening velocity was 5 times faster than fascicle velocity (37.5 versus 7.4 cm s-1, P<0.01). Steeper incline skiing was achieved by greater muscle activity (24%, P=0.04) and slower fascicle shortening velocity (3.4 versus 4.5 cm s-1, P<0.01). Faster speed was achieved by greater peak muscle activity (23%, P<0.01) and no change in fascicle shortening velocity. Our data show that, during diagonal-style cross-county skiing, muscle behaviour is uncoupled from the joint movement, which enables beneficial contractile conditions and energy utilisation with different slopes and speeds. Active preloading at the end of the glide phase may facilitate these mechanisms.

Effect of Forearm Postures and Elbow Joint Angles on Elbow Flexion Torque and Mechanomyography in Neuromuscular Electrical Stimulation of the Biceps Brachii.

Neuromuscular electrical stimulation plays a pivotal role in rehabilitating muscle function among individuals with neurological impairment. However, there remains uncertainty regarding whether the muscle's response to electrical excitation is affected by forearm posture, joint angle, or a combination of both factors. This study aimed to investigate the effects of forearm postures and elbow joint angles on the muscle torque and MMG signals. Measurements of the torque around the elbow and MMG of the biceps brachii (BB) muscle were conducted in 36 healthy subjects (age, 22.24 ± 2.94 years; height, 172 ± 0.5 cm; and weight, 67.01 ± 7.22 kg) using an in-house elbow flexion testbed and neuromuscular electrical stimulation (NMES) of the BB muscle. The BB muscle was stimulated while the forearm was positioned in the neutral, pronation, or supination positions. The elbow was flexed at angles of 10°, 30°, 60°, and 90°. The study analyzed the impact of the forearm posture(s) and elbow joint angle(s) on the root-mean-square value of the torque (TQRMS). Subsequently, various MMG parameters, such as the root-mean-square value (MMGRMS), the mean power frequency (MMGMPF), and the median frequency (MMGMDF), were analyzed along the longitudinal, lateral, and transverse axes of the BB muscle fibers. The test-retest interclass correlation coefficient (ICC21) for the torque and MMG ranged from 0.522 to 0.828. Repeated-measure ANOVAs showed that the forearm posture and elbow flexion angle significantly influenced the TQRMS (p < 0.05). Similarly, the MMGRMS, MMGMPF, and MMGMDF showed significant differences among all the postures and angles (p < 0.05). However, the combined main effect of the forearm posture and elbow joint angle was insignificant along the longitudinal axis (p > 0.05). The study also found that the MMGRMS and TQRMS increased with increases in the joint angle from 10° to 60° and decreased at greater angles. However, during this investigation, the MMGMPF and MMGMDF exhibited a consistent decrease in response to increases in the joint angle for the lateral and transverse axes of the BB muscle. These findings suggest that the muscle contraction evoked by NMES may be influenced by the interplay between actin and myosin filaments, which are responsible for muscle contraction and are, in turn, influenced by the muscle length. Because restoring the function of limbs is a common goal in rehabilitation services, the use of MMG in the development of methods that may enable the real-time tracking of exact muscle dimensional changes and activation levels is imperative.

Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2.

The ACTN2 gene encodes α-actinin 2, located in the Z-disc of the sarcomeres in striated muscle. In this study, we sought to investigate the effects of an ACTN2 missense variant of unknown significance (p.A868T) on cardiac muscle structure and function. Left ventricular free wall samples were obtained at the time of cardiac transplantation from a heart failure patient with the ACTN2 A868T heterozygous variant. This variant is in the EF 3-4 domain known to interact with titin and α-actinin. At the ultrastructural level, ACTN2 A868T cardiac samples presented small structural changes in cardiomyocytes when compared to healthy donor samples. However, contractile mechanics of permeabilized ACTN2 A868T variant cardiac tissue displayed higher myofilament Ca2+ sensitivity of isometric force, reduced sinusoidal stiffness, and faster rates of tension redevelopment at all Ca2+ levels. Small-angle X-ray diffraction indicated increased separation between thick and thin filaments, possibly contributing to changes in muscle kinetics. Molecular dynamics simulations indicated that while the mutation does not significantly impact the structure of α-actinin on its own, it likely alters the conformation associated with titin binding. Our results can be explained by two Z-disc mediated communication pathways: one pathway that involves α-actinin's interaction with actin, affecting thin filament regulation, and the other pathway that involves α-actinin's interaction with titin, affecting thick filament activation. This work establishes the role of α-actinin 2 in modulating cross-bridge kinetics and force development in the human myocardium as well as how it can be involved in the development of cardiac disease.

An Acute Transition from Rearfoot to Forefoot Strike does not Induce Major Changes in Plantarflexor Muscles Activation for Habitual Rearfoot Strike Runners.

Footstrike pattern has received increased attention within the running community because there is a common belief that forefoot strike running (FFS) is more advantageous (i.e., improve performance and reduce running injuries) than rearfoot strike running (RFS) in distance running. Literature reports suggest greater knee joint flexion magnitude and initial knee angle during stance in FFS compared with RFS running We examined the EMG activation of the triceps surae muscles during an acute transition from RFS to FFS strike. We tested the hypothesis that due to larger knee flexion in FFS the gastrocnemius muscles possibly decrease their EMG activity because muscle fascicles operate under unfavorable conditions. Fourteen competitive healthy middle- and long-distance runners who were habitual RFS runners ran on a treadmill at three speeds: 12, 14, and 16 km·h-1. Each running speed was performed with both FFS and RFS patterns. Lower limb kinematics in the sagittal plane and normalized electromyography (EMG) activity of medial gastrocnemius proximal, middle and distal regions, lateral gastrocnemius and soleus muscles were compared between footstrike patterns and running speeds across the stride cycle. Contrary to our expectations, the knee joint range of motion was similar in FFS and RFS running. However, the sagittal plane ankle joint motion was greater (p < 0.01) while running with FFS, resulting in a significantly greater muscle-tendon unit lengthening (p < 0.01) in FFS compared with RFS running. In addition, medial and lateral gastrocnemius showed higher EMG activity in FFS compared with RFS running in the late swing and early stance but only for a small percentage of the stride cycle. However, strike patterns and running speed failed to induce region-specific activation differences within the medial gastrocnemius muscle. Overall, well-trained RFS runners are able to change to FFS running by altering only the ankle joint kinematics without remarkably changing the EMG activity pattern.

Shortening deactivation: quantifying a critical component of cyclical muscle contraction.

A muscle undergoing cyclical contractions requires fast and efficient muscle activation and relaxation to generate high power with relatively low energetic cost. To enhance activation and increase force levels during shortening, some muscle types have evolved stretch activation (SA), a delayed increased in force following rapid muscle lengthening. SA's complementary phenomenon is shortening deactivation (SD), a delayed decrease in force following muscle shortening. SD increases muscle relaxation, which decreases resistance to subsequent muscle lengthening. Although it might be just as important to cyclical power output, SD has received less investigation than SA. To enable mechanistic investigations into SD and quantitatively compare it to SA, we developed a protocol to elicit SA and SD from Drosophila and Lethocerus indirect flight muscles (IFM) and Drosophila jump muscle. When normalized to isometric tension, Drosophila IFM exhibited a 118% SD tension decrease, Lethocerus IFM dropped by 97%, and Drosophila jump muscle decreased by 37%. The same order was found for normalized SA tension: Drosophila IFM increased by 233%, Lethocerus IFM by 76%, and Drosophila jump muscle by only 11%. SD occurred slightly earlier than SA, relative to the respective length change, for both IFMs; but SD was exceedingly earlier than SA for jump muscle. Our results suggest SA and SD evolved to enable highly efficient IFM cyclical power generation and may be caused by the same mechanism. However, jump muscle SA and SD mechanisms are likely different, and may have evolved for a role other than to increase the power output of cyclical contractions.

The mechanical properties of the mantle muscle of European cuttlefish (Sepia officinalis).

The circular muscles surrounding the mantle cavity of European cuttlefish (Sepia officinalis) generate the mechanical power to compress the cavity, forcing a jet of water out of the funnel, propelling the animal during jet propulsion swimming. During ontogeny, jetting frequency decreases in adults compared with juveniles, and this is expected to be reflected in the contractile properties of the locomotory muscles. To develop greater insight into how the locomotion of these animals is powered during ontogeny, we determined the mechanical properties of bundles of muscle fascicles during isometric, isotonic and cyclic length changes in vitro, at two life stages: juveniles and adults. The twitch kinetics were faster in juveniles than in adults (twitch rise time 257 ms compared with 371 ms; half-twitch relaxation 257 ms compared with 677 ms in juveniles and adults, respectively); however, twitch and tetanic stress, the maximum velocity of shortening and curvature of the force-velocity relationship did not differ. Under cyclic conditions, net power exhibited an inverted U-shaped relationship with cycle frequency in both juveniles and adults; the frequency at which maximum net power was achieved was shifted to lower cycle frequencies with increased maturity, which is consistent with the slower contraction and relaxation kinetics in adults compared with juveniles. The cycle frequency at which peak power was achieved during cyclical contractions in vitro was found to match that seen in vivo in juveniles, suggesting power is being maximised during jet propulsion swimming.