Trade-offs in muscle physiology in selectively bred high runner mice.

A trade-off between locomotor speed and endurance occurs in various taxa, and is thought to be underpinned by a muscle-level trade-off. Among four replicate high runner (HR) lines of mice, selectively bred for voluntary wheel-running behavior, a negative correlation between average running speed and time spent running has evolved. We hypothesize that this trade-off is due to changes in muscle physiology. We studied the HR lines at generation 90, at which time one line (L3) is fixed for the mini-muscle phenotype, another is polymorphic (L6) and the others (L7, L8) lack mini-muscle individuals. We used in situ preparations to quantify the contractile properties of the triceps surae muscle complex. Maximal shortening velocity varied significantly, being lowest in mini-muscle mice (L3 mini=25.2 mm s-1, L6 mini=25.5 mm s-1), highest in normal-muscle mice L6 and L8 (40.4 and 50.3 mm s-1, respectively) and intermediate in normal-muscle L7 mice (37.2 mm s-1). Endurance, measured both as the slope of the decline in force and the proportion of initial force that could be sustained, also varied significantly. The slope was shallowest in mini-muscle mice (L3 mini=-0.00348, L6 mini=-0.00238), steepest in lines L6 and L8 (-0.01676 and -0.01853), and intermediate in L7 (-0.01145). Normalized sustained force was highest in mini-muscle mice (L3 mini=0.98, L6 mini=0.92) and lowest in L8 (0.36). There were significant, negative correlations between velocity and endurance metrics, indicating a muscle-level trade-off. However, this muscle-level trade-off does not seem to underpin the organismal-level speed and endurance trade-off previously reported as the ordering of the lines is reversed: the lines that run the fastest for the least time have the lowest muscle complex velocity and highest endurance.

The Multi-Scale, Three-Dimensional Nature of Skeletal Muscle Contraction.

Muscle contraction is a three-dimensional process, as anyone who has observed a bulging muscle knows. Recent studies suggest that the three-dimensional nature of muscle contraction influences its mechanical output. Shape changes and radial forces appear to be important across scales of organization. Muscle architectural gearing is an emerging example of this process.

In vivo force-length and activation dynamics of two distal rat hindlimb muscles in relation to gait and grade.

Muscle function changes to meet the varying mechanical demands of locomotion across different gait and grade conditions. A muscle's work output is determined by time-varying patterns of neuromuscular activation, muscle force and muscle length change, but how these patterns change under different conditions in small animals is not well defined. Here, we report the first integrated in vivo force-length and activation patterns in rats, a commonly used small animal model, to evaluate the dynamics of two distal hindlimb muscles (medial gastrocnemius and plantaris) across a range of gait (walk, trot and gallop) and grade (level and incline) conditions. We use these data to explore how the pattern of force production, muscle activation and muscle length changes across conditions in a small quadrupedal mammal. As hypothesized, we found that the rat muscles show limited fascicle strains during active force generation in stance across gaits and grades, indicating that these distal rat muscles generate force economically but perform little work, similar to patterns observed in larger animals during level locomotion. Additionally, given differences in fiber type composition and variation in motor unit recruitment across the gait and grade conditions examined here for these muscles, the in vivo force-length behavior and neuromuscular activation data reported here can be used to validate improved two-element Hill-type muscle models.

Stuck in gear: age-related loss of variable gearing in skeletal muscle.

Skeletal muscles power a broad diversity of animal movements, despite only being able to produce high forces over a limited range of velocities. Pennate muscles use a range of gear ratios, the ratio of muscle shortening velocity to fiber shortening velocity, to partially circumvent these force-velocity constraints. Muscles operate with a high gear ratio at low forces; fibers rotate to greater angles of pennation, enhancing velocity but compromising force. At higher forces, muscles operate with a lower gear ratio; fibers rotate little so limiting muscle shortening velocity, but helping to preserve force. This ability to shift gears is thought to be due to the interplay of contractile force and connective tissue constraints. In order to test this hypothesis, gear ratios were determined in the medial gastrocnemius muscles of both healthy young rats, and old rats where the interaction between contractile and connective tissue properties was assumed to be disrupted. Muscle fiber and aponeurosis stiffness increased with age (P<0.05) from 19.1±5.0 kPa and 188.5±24.2 MPa, respectively, in young rats to 39.1±4.2 kPa and 328.0±48.3 MPa in old rats, indicating a mechanical change in the interaction between contractile and connective tissues. Gear ratio decreased with increasing force in young (P<0.001) but not old (P=0.72) muscles, indicating that variable gearing is lost in old muscle. These findings support the hypothesis that variable gearing results from the interaction between contractile and connective tissues and suggest novel explanations for the decline in muscle performance with age.

The energetic benefits of tendon springs in running: is the reduction of muscle work important?

The distal muscle-tendon units of cursorial species are commonly composed of short muscle fibres and long, compliant tendons. It is assumed that the ability of these tendons to store and return mechanical energy over the course of a stride, thus avoiding the cyclic absorption and regeneration of mechanical energy by active muscle, offers some metabolic energy savings during running. However, this assumption has not been tested directly. We used muscle ergometry and myothermic measurements to determine the cost of force production in muscles acting isometrically, as they could if mechanical energy was stored and returned by tendon, and undergoing active stretch-shorten cycles, as they would if mechanical energy was absorbed and regenerated by muscle. We found no detectable difference in the cost of force production in isometric cycles compared with stretch-shorten cycles. This result suggests that replacing muscle stretch-shorten work with tendon elastic energy storage and recovery does not reduce the cost of force production. This calls into question the assumption that reduction of muscle work drove the evolution of long distal tendons. We propose that the energetic benefits of tendons are derived primarily from their effect on muscle and limb architecture rather than their ability to reduce the cyclic work of muscle.

What drives activation-dependent shifts in the force-length curve?

Skeletal muscles are rarely recruited maximally during movement. However, much of our understanding of muscle properties is based on studies using maximal activation. The effect of activation level on skeletal muscle properties remains poorly understood. Muscle optimum length increases with decreased activation; however, the mechanism responsible is unclear. Here, we attempted to determine whether length-dependent calcium effects, or the effect of absolute force underpin this shift. Fixed-end contractions were performed in frog plantaris muscles at a range of lengths using maximal tetanic (high force, high calcium), submaximal tetanic (low force, high calcium) and twitch (low force, low calcium) stimulation conditions. Peak force and optimum length were determined in each condition. Optimum length increased with decreasing peak force, irrespective of stimulation condition. Assuming calcium concentration varied as predicted, this suggests that absolute force, rather than calcium concentration, underpins the effect of activation level on optimum length. We suggest that the effect of absolute force is due to the varying effect of the internal mechanics of the muscle at different activation levels. These findings have implications for our understanding of in vivo muscle function and suggest that mechanical interactions within muscle may be important determinants of force at lower levels of activation.

The effect of muscle ultrastructure on the force, displacement and work capacity of skeletal muscle.

Skeletal muscle powers animal movement through interactions between the contractile proteins, actin and myosin. Structural variation contributes greatly to the variation in mechanical performance observed across muscles. In vertebrates, gross structural variation occurs in the form of changes in the muscle cross-sectional area : fibre length ratio. This results in a trade-off between force and displacement capacity, leaving work capacity unaltered. Consequently, the maximum work per unit volume-the work density-is considered constant. Invertebrate muscle also varies in muscle ultrastructure, i.e. actin and myosin filament lengths. Increasing actin and myosin filament lengths increases force capacity, but the effect on muscle fibre displacement, and thus work, capacity is unclear. We use a sliding-filament muscle model to predict the effect of actin and myosin filament lengths on these mechanical parameters for both idealized sarcomeres with fixed actin : myosin length ratios, and for real sarcomeres with known filament lengths. Increasing actin and myosin filament lengths increases stress without reducing strain capacity. A muscle with longer actin and myosin filaments can generate larger force over the same displacement and has a higher work density, so seemingly bypassing an established trade-off. However, real sarcomeres deviate from the idealized length ratio suggesting unidentified constraints or selective pressures.

The effects of asymmetric length trajectories on the initial mechanical efficiency of mouse soleus muscles.

Asymmetric cycles with more than half of the cycle spent shortening enhance the mechanical power output of muscle during flight and vocalisation. However, strategies that enhance muscle mechanical power output often compromise efficiency. In order to establish whether a trade-off necessarily exists between power and efficiency, we investigated the effects of asymmetric muscle length trajectories on the maximal mechanical cycle-average power output and initial mechanical efficiency (E(i)). Work and heat were measured in vitro in a mouse soleus muscle undergoing contraction cycles with 25% (Saw25%), 50% (Saw50%) and 75% (Saw75%) of the cycles spent shortening. Cycle-average power output tended to increase with the proportion of the cycle spent shortening at a given frequency. Maximum cycle-average power output was 102.9±7.6 W kg(-1) for Saw75% cycles at 5 Hz. E(i) was very similar for Saw50% and Saw75% cycles at all frequencies (approximately 0.27 at 5 Hz). Saw25% cycles had E(i) values similar to those of Saw50% and Saw75% cycles at 1 Hz (approximately 0.20), but were much less efficient at 5 Hz (0.08±0.03). The lower initial mechanical efficiency of Saw25% cycles at higher frequencies suggests that initial mechanical efficiency is reduced if the time available for force generation and relaxation during shortening is insufficient. The similar initial mechanical efficiency of Saw50% and Saw75% cycles at all frequencies shows that increasing the proportion of the contraction cycle spent shortening is a strategy that allows an animal to increase muscle mechanical power output without compromising initial mechanical efficiency.

Locomotion on a slope in leaf-cutter ants: metabolic energy use, behavioural adaptations and the implications for route selection on hilly terrain.

The metabolic cost of the negotiation of obstacles, and the influence that this has on route selection, are important determinants of an animal's locomotor behaviour. We determined the gross metabolic cost of locomotion on slopes of different gradients, ranging from -90 to +90 deg, in leaf-cutter ants (Acromyrmex octospinosus) in a closed-circuit respirometry system. Ants were able to select their preferred speed for each gradient. The gross metabolic energy expenditure per unit distance travelled on the slope (C(path)) was calculated from the rate of CO(2) production and the speed of locomotion. These data were used to predict the optimal slopes for minimising the vertical cost of locomotion and vertical journey time. The gross rate of CO(2) production was approximately constant (1.7 ml g(-1) h(-1)) and was not significantly affected by slope. Ants moderated their speed with slope (P<0.05), travelling the fastest during level locomotion (2.0±0.1 cm s(-1), N=20) and increasingly slowly with increased gradient (both on an incline and a decline). C(path) varied significantly with slope, being lowest during level locomotion (646.0±51.2 J kg(-1) m(-1)) and increasing with increasing gradient. These results suggest that ants adapt their locomotor behaviour to keep metabolic rate constant despite changing mechanical demands. It is predicted that when undertaking a journey involving vertical displacement that ants will select routes with a gradient of between 51 and 57 deg during ascent and with a gradient of between -45 and -51 deg during descent, in order to minimise both vertical journey time and vertical cost of locomotion.

Elastic energy storage and the efficiency of movement.

Movement is an integral part of animal biology. It enables organisms to escape from danger, acquire food, and perform courtship displays. Changing the speed or vertical position of a body requires mechanical energy. This energy is typically provided by the biological motor, striated muscle. Striated muscle uses chemical (metabolic) energy to produce force, to move this force over a distance to do work, and to do this work within some time to generate power. The metabolic energy consumed in producing these mechanical outputs is a major component of an organism's energy budget, particularly during repetitive, cyclical movements. This energy could otherwise be used for maintenance, growth, and reproduction. Hence, fitness may be enhanced by improving locomotor efficiency - the ratio between work done and metabolic energy consumed. This may be achieved by reducing the need for muscle to do work, and by increasing the efficiency with which muscle does work.

Beyond bouncy gaits: The role of multiscale compliance in skeletal muscle performance.

McNeill Alexander demonstrated that compliant tendons could improve locomotor performance by decoupling muscle length changes from joint movements and mechanical energy fluctuations. This was revolutionary for our understanding of animal locomotion, but also highlighted the limitations of our understanding of the contractile performance of muscle under the dynamic conditions relevant to movement. This review addresses the potential for biological compliance to not only alter the demands on muscle but also fundamentally change contractile performance. Compliance exists across all spatial scales within the muscle. Molecule scale compliance is observed in the thin filament and the cytoskeletal protein titin likely acts as an activation-dependent variable-stiffness spring. Larger scale connective tissue compliance is found not only in tendons but also the more structurally complex extracellular matrix and aponeuroses. The interaction of the compliance in these structures with the contractile elements of muscle, and the variation in this interaction across physiological conditions, appears to explain muscle phenomena central to locomotion but not readily explained by the crossbridge and sliding filament theories, such as history dependence, the energetics of cyclical contractions, the nonlinear effect of activation level on muscle performance and the effect of age on muscle and locomotor capacity.

Tuning of feedforward control enables stable muscle force-length dynamics after loss of autogenic proprioceptive feedback.

Animals must integrate feedforward, feedback and intrinsic mechanical control mechanisms to maintain stable locomotion. Recent studies of guinea fowl (Numida meleagris) revealed that the distal leg muscles rapidly modulate force and work output to minimize perturbations in uneven terrain. Here we probe the role of reflexes in the rapid perturbation responses of muscle by studying the effects of proprioceptive loss. We induced bilateral loss of autogenic proprioception in the lateral gastrocnemius muscle (LG) using self-reinnervation. We compared in vivo muscle dynamics and ankle kinematics in birds with reinnervated and intact LG. Reinnervated and intact LG exhibit similar steady state mechanical function and similar work modulation in response to obstacle encounters. Reinnervated LG exhibits 23ms earlier steady-state activation, consistent with feedforward tuning of activation phase to compensate for lost proprioception. Modulation of activity duration is impaired in rLG, confirming the role of reflex feedback in regulating force duration in intact muscle.

Modeling age-related changes in muscle-tendon dynamics during cyclical contractions in the rat gastrocnemius.

Efficient muscle-tendon performance during cyclical tasks is dependent on both active and passive mechanical tissue properties. Here we examine whether age-related changes in the properties of muscle-tendon units (MTUs) compromise their ability to do work and utilize elastic energy storage. We empirically quantified passive and active properties of the medial gastrocnemius muscle and material properties of the Achilles tendon in young (∼6 mo) and old (∼32 mo) rats. We then used these properties in computer simulations of a Hill-type muscle model operating in series with a Hookean spring. The modeled MTU was driven through sinusoidal length changes and activated at a phase that optimized muscle-tendon tuning to assess the relative contributions of active and passive elements to the force and work in each cycle. In physiologically realistic simulations where young and old MTUs started at similar passive forces and developed similar active forces, the capacity of old MTUs to store elastic energy and produce positive work was compromised. These results suggest that the observed increase in the metabolic cost of locomotion with aging may be in part due to the recruitment of additional muscles to compensate for the reduced work at the primary MTU. Furthermore, the age-related increases in passive stiffness coupled with a reduced active force capacity in the muscle can lead to shifts in the force-length and force-velocity operating range that may significantly impact mechanical and metabolic performance. Our study emphasizes the importance of the interplay between muscle and tendon mechanical properties in shaping MTU performance during cyclical contractions.