Search

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.

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.

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.

Biological movement is an inherently dynamic process, characterized by large spatiotemporal variations in force and mechanical energy. Molecular level interactions between the contractile proteins actin and myosin do work, generating forces and transmitting them to the environment via the muscle's and supporting tissues' complex structures. Most existing theories of muscle contraction are derived from observations of muscle performance under simple, tightly controlled, in vitro or in situ conditions. These theories provide predictive power that falls off as we examine the more complicated action and movement regimes seen in biological movement. Our early and heavy focus on actin and myosin interactions have lead us to overlook other interactions and sources of force regulation. It increasingly appears that the structural heterogeneity, and micro-to-macro spatial scales of the force transmission pathways that exist between actin and myosin and the environment, determine muscle performance in ways that manifest most clearly under the dynamic conditions occurring during biological movement. Considering these interactions, along with the dynamics of force transmission tissues, actuators, and environmental physics have enriched our understanding of biological motion and force generation. This symposium brings together diverse investigators to consolidate our understanding of the role of spatial scale and structural heterogeneity role in muscle performance, with the hope of updating frameworks for understanding muscle contraction and predicting muscle performance in biological movement.

The collagenous extracellular matrix (ECM) of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance. Here we combine a mathematical model and experimental manipulations to examine how changes in the mechanical properties of the ECM constrain the ability of muscle fibers and fascicles to radially expand and how such a constraint may limit active muscle shortening. We model the mechanical interaction between a contracting muscle and the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model shows that as the proportion of a muscle cross section made up of ECM increases, the muscle's ability to expand radially is compromised, which in turn restricts muscle shortening. In our experiments, we use a physical constraint placed around the muscle to restrict radial expansion during a contraction. Our experimental results are consistent with model predictions and show that muscles restricted from radial expansion undergo less shortening and generate less mechanical work under identical loads and stimulation conditions. This work highlights the intimate mechanical interaction between contractile and connective tissue structures within skeletal muscle and shows how a deviation from a healthy, well-tuned relationship can compromise performance.

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, MG and plantaris, PL) across a range of gait (walk, trot, and gallop) and grade (level versus 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.

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 response 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 ankle kinematics andin vivomuscle dynamics in birds with reinnervated LG and intact LG. Reinnervated and intact muscles exhibit similar force-length dynamics, with rapid changes in work to stabilize running obstacle terrain. Reinnervated LG exhibits 23ms earlier steady-state activation, consistent with feedforward tuning of activation phase to compensate for lost proprioception. Modulation of force duration is impaired in rLG, confirming the role of reflex feedback in regulating force duration in intact muscle.

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.

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

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.

Skeletal muscle force is generated by cross-bridge interactions between the overlapping contractile proteins, actin and myosin. The geometry of this overlap gives us the force-length relationship in which maximum isometric force is generated at an intermediate, optimum, length. However, the force-length relationship is not constant; optimum length increases with decreasing muscle activation. This effect is not predicted from actin-myosin overlap. Here we present evidence that this activation-dependent shift in optimum length may be due to a series compliance within muscles. As muscles generate force during fixed-end contractions, fibers shorten against series compliance until forces equilibrate and they become isometric. Shortening against series-compliance is proportional to activation, and creates conditions under which shortening-induced force depression may suppress full force development. Greater shortening will result in greater force depression. Hence, optimum length may decrease as activation rises due to greater fiber shortening. We discuss explanations of such history dependence, giving a review of previously proposed processes and suggesting a novel mechanistic explanation for the most likely candidate process based on tropomyosin kinetics. We suggest this mechanism could change the relationship between actin-myosin overlap and cross-bridge binding potential, not only depressing force at any given length, but also altering the relationship between force and length. This would have major consequences for our understanding of in vivo muscle performance.

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 CO2 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 CO2 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

SUMMARYAsymmetric 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 (Ei). 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. Ei was very similar for Saw50% and Saw75% cycles at all frequencies (approximately 0.27 at 5 Hz). Saw25% cycles had Ei 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.

Collective animal behaviour has attracted much attention recently, but cause-and-effect within interaction sequences has often been difficult to establish. To tackle this problem, we constructed a robotic fish (‘Robofish’) with which three-spined sticklebacks (Gasterosteus aculeatus L.) interact. Robofish is a computer-controlled replica stickleback that can be programmed to move around a tank. First, we demonstrated the functioning of the method: that the sticklebacks interacted with Robofish. We examined two types of interaction: recruitment and leadership. We found that Robofish could recruit a single fish from a refuge and could initiate a turn in singletons and in groups of ten, i.e. act as a leader. We also showed that the influence of Robofish diminished after the first 30 min that fish spent in a new environment. Second, using this method, we investigated the effects of metric and topological inter-individual distance on the influence that Robofish had on the orientation of fish in a shoal of ten. We found that inter-individual interactions during this turn were predominantly mediated by topological, rather than metric, distance. Finally, we discussed the potential of this novel method and the importance of our findings for the study of collective animal behaviour.

Skeletal muscle exhibits broad functional diversity, despite its inherent length and velocity constraints. The observed variation in morphology and physiology is assumed to have evolved to allow muscle to operate at its optimal length and velocity during locomotion. Here, we used the variation in optimum lengths and velocities that occurs with muscle activation level to experimentally test this assumption. Muscle ergometry and sonomicrometry were used to characterize force–length and power–velocity relationships, andin vivooperating lengths and velocities, at a range of activation levels. Operating lengths and velocities were mapped onto activation level specific force–length and power–velocity relationships to determine whether they tracked changing optima. Operating velocities decreased in line with decreased optimal velocities, suggesting that optimal velocities are always used. However, operating lengths did not change with changing optima. At high activation levels, fibres used an optimal range of lengths. However, at lower activation levels, fibres appeared to operate on the ascending limb of sub-maximally activated force–length relationships. This suggests that optimal lengths are only used when demand is greatest. This study provides the first mapping of operating lengths to activation level-specific optima, and as such, provides insight into our assumptions about the factors that determine muscle performance during locomotion.

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 proposed that the energetic benefits of tendons are derived primarily from their effect on muscle and limb architecture rather than their ability to reduce cyclic muscle work.

The output of skeletal muscle can be varied by selectively recruiting different motor units. However, our knowledge of muscle function is largely derived from muscle in which all motor units are activated. This discrepancy may limit our understanding ofin vivomuscle function. Hence, this study aimed to characterize the mechanical properties of muscle with different motor unit activation. We determined the isometric properties and isotonic force–velocity relationship of rat plantaris musclesin situwith all of the muscle active, 30% of the muscle containing predominately slower motor units active or 20% of the muscle containing predominately faster motor units active. There was a significant effect of active motor unit type on isometric force rise time (p< 0.001) and the force–velocity relationship (p< 0.001). Surprisingly, force rise time was longer and maximum shortening velocity higher when all motor units were active than when either fast or slow motor units were selectively activated. We propose this is due to the greater relative effects of factors such as series compliance and muscle resistance to shortening during sub-maximal contractions. The findings presented here suggest that recruitment according to the size principle, where slow motor units are activated first and faster ones recruited as demand increases, may not pose a mechanical paradox, as has been previously suggested.

Background\ud \ud Fibrillins 1 (FBN1) and 2 (FBN2) are components of microfibrils, microfilaments that are present in many connective tissues, either alone or in association with elastin. Marfan's syndrome and congenital contractural arachnodactyly (CCA) result from dominant mutations in the genes FBN1 and FBN2 respectively. Patients with both conditions often present with specific muscle atrophy or weakness, yet this has not been reported in the mouse models. In the case of Fbn1, this is due to perinatal lethality of the homozygous null mice making measurements of strength difficult. In the case of Fbn2, four different mutant alleles have been described in the mouse and in all cases syndactyly was reported as the defining phenotypic feature of homozygotes.\ud \ud Methodology/Principal Findings\ud \ud As part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified a mouse mutant, Mariusz, which exhibited muscle weakness along with hindlimb syndactyly. We identified an amber nonsense mutation in Fbn2 in this mouse mutant. Examination of a previously characterised Fbn2-null mutant, Fbn2fp, identified a similar muscle weakness phenotype. The two Fbn2 mutant alleles complement each other confirming that the weakness is the result of a lack of Fbn2 activity. Skeletal muscle from mutants proved to be abnormal with higher than average numbers of fibres with centrally placed nuclei, an indicator that there are some regenerating muscle fibres. Physiological tests indicated that the mutant muscle produces significantly less maximal force, possibly as a result of the muscles being relatively smaller in Mariusz mice.\ud \ud Conclusions\ud \ud These findings indicate that Fbn2 is involved in integrity of structures required for strength in limb movement. As human patients with mutations in the fibrillin genes FBN1 and FBN2 often present with muscle weakness and atrophy as a symptom, Fbn2-null mice will be a useful model for examining this aspect of the disease process further.