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Skeletal muscles are length- and velocity-sensitive force producers, constructed of a vast array of sarcomeres. Muscles come in a variety of sizes and shapes to accomplish a wide variety of tasks. How does muscle design match task performance? In this review, we outline muscle's basic properties and strategies that are used to produce movement. Several examples are provided, primarily for human muscles, in which skeletal muscle architecture and moment arms are tailored to a particular performance requirement. In addition, the concept that muscles may have a preferred sarcomere length operating range is also introduced. Taken together, the case is made that muscles can be fine-tuned to perform specific tasks that require actuators with a wide range of properties.

Computer models that estimate the force generation capacity of lower limb muscles have become widely used to simulate the effects of musculoskeletal surgeries and create dynamic simulations of movement. Previous lower limb models are based on severely limited data describing limb muscle architecture (i.e., muscle fiber lengths, pennation angles, and physiological cross-sectional areas). Here, we describe a new model of the lower limb based on data that quantifies the muscle architecture of 21 cadavers. The model includes geometric representations of the bones, kinematic descriptions of the joints, and Hill-type models of 44 muscle–tendon compartments. The model allows calculation of muscle–tendon lengths and moment arms over a wide range of body positions. The model also allows detailed examination of the force and moment generation capacities of muscles about the ankle, knee, and hip and is freely available at www.simtk.org .

Skeletal muscle architecture is defined as the arrangement of fibers in a muscle and functionally defines performance capacity. Architectural values are used to model muscle-joint behavior and to make surgical decisions. The two most extensively used human lower extremity data sets consist of five total specimens of unknown size, gender, and age. Therefore, it is critically important to generate a high-fidelity human lower extremity muscle architecture data set. We disassembled 27 muscles from 21 human lower extremities to characterize muscle fiber length and physiologic cross-sectional area, which define the excursion and force-generating capacities of a muscle. Based on their architectural features, the soleus, gluteus medius, and vastus lateralis are the strongest muscles, whereas the sartorius, gracilis, and semitendinosus have the largest excursion. The plantarflexors, knee extensors, and hip adductors are the strongest muscle groups acting at each joint, whereas the hip adductors and hip extensors have the largest excursion. Contrary to previous assertions, two-joint muscles do not necessarily have longer fibers than single-joint muscles as seen by the similarity of knee flexor and extensor fiber lengths. These high-resolution data will facilitate the development of more accurate musculoskeletal models and challenge existing theories of muscle design; we believe they will aid in surgical decision making.

PurposeThe purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis.MethodsMultifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini–Hochberg) and for between-group post hoc comparisons (Sidak) were applied.ResultsAdipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012).ConclusionIndividuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Exercise‐induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise‐induced phenotypes. Using this network, we formulated a logic‐based ordinary differential equation model predicting time‐dependent molecular and phenotypic alterations following acute endurance and resistance exercises. Compared with nine independent studies, the model accurately predicted 18/21 (85%) acute responses to resistance exercise and 12/16 (75%) acute responses to endurance exercise. Detailed sensitivity analysis of differential phenotypic responses to resistance and endurance training showed that, in the model, exercise regulates cell growth and protein synthesis primarily by signalling via mechanistic target of rapamycin, which is activated by Akt and inhibited in endurance exercise by AMP‐activated protein kinase. Endurance exercise preferentially activates inflammation via reactive oxygen species and nuclear factor κB signalling. Furthermore, the expected preferential activation of mitochondrial biogenesis by endurance exercise was counterbalanced in the model by protein kinase C in response to resistance training. This model provides a new tool for investigating cross‐talk between skeletal muscle signalling pathways activated by endurance and resistance exercise, and the mechanisms of interactions such as the interference effects of endurance training on resistance exercise outcomes. What is the central question of this study? How do the cell signalling pathways regulating skeletal myocyte responses to resistance and endurance exercise interact? What is the main finding and its importance? A new systems model of skeletal muscle signalling pathways activated by resistance and endurance training was developed with eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise‐induced phenotypes. The model accurately predicted 85% of independent measurements for resistance exercise and 75% for endurance training. Analysis revealed pathways regulating the preferential activation of protein synthesis and cell growth by resistance training and inflammation by endurance exercise.

Background Magnetic Resonance Imaging (MRI) is commonly used to assess the health of the lumbar spine and supporting structures. Studies have suggested that fatty infiltration of the posterior lumbar muscles is important in predicting responses to treatment for low back pain. However, methodological differences exist in defining the region of interest (ROI) of a muscle, which limits the ability to compare data between studies. The purpose of this study was to determine reliability and systematic differences within and between two commonly utilized methodologies for ROI definitions of lumbar paraspinal muscle. Methods T2-weighted MRIs of the mid-L4 vertebrae from 37 patients with low back pain who were scheduled for lumbar spine surgery were included from a hospital database. Fatty infiltration for these patients ranged from low to high, based on Kjaer criteria. Two methods were used to define ROI: 1) segmentation of the multifidus and erector spinae based on fascial planes including epimuscular fat, and 2) segmentation of the multifidus and erector spinae based on visible muscle boundaries, which did not include epimuscular fat. Total cross sectional area (tCSA), fat signal fraction (FSF), muscle cross sectional area, and fat cross sectional area were measured. Degree of agreement between raters for each parameter was assessed using intra-class correlation coefficients (ICC) and area fraction of overlapping voxels. Results Excellent inter-rater agreement (ICC > 0.75) was observed for all measures for both methods. There was no significant difference between area fraction overlap of ROIs between methods. Method 1 demonstrated a greater tCSA for both the erector spinae (14–15%, p  < 0.001) and multifidus (4%, p  < 0.016) but a greater FSF only for the erector spinae (11–13%, p < 0.001). Conclusion The two methods of defining lumbar spine muscle ROIs demonstrated excellent inter-rater reliability, although significant differences exist as method 1 showed larger CSA and FSF values compared to method 2. The results of this study confirm the validity of using either method to measure lumbar paraspinal musculature, and that method should be selected based on the primary outcome variables of interest.

Background Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP). Methods Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson’s correlation test. Results No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation ( p  > 0.31). However, patients reported reduced pain ( p  = 0.002) and were stronger ( p  = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength. Conclusion While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.

An a priori model of the whole active muscle length-tension relationship was constructed utilizing only myofilament length and serial sarcomere number for rabbit tibialis anterior (TA), extensor digitorum longus (EDL), and extensor digitorum II (EDII) muscles. Passive tension was modeled with a two-element Hill-type model. Experimental length-tension relations were then measured for each of these muscles and compared to predictions. The model was able to accurately capture the active-tension characteristics of experimentally-measured data for all muscles (ICC=0.88±0.03). Despite their varied architecture, no differences in predicted versus experimental correlations were observed among muscles. In addition, the model demonstrated that excursion, quantified by full-width-at-half-maximum (FWHM) of the active length-tension relationship, scaled linearly (slope=0.68) with normalized muscle fiber length. Experimental and theoretical FWHM values agreed well with an intraclass correlation coefficient of 0.99 ( p<0.001). In contrast to active tension, the passive tension model deviated from experimentally-measured values and thus, was not an accurate predictor of passive tension (ICC=0.70±0.07). These data demonstrate that modeling muscle as a scaled sarcomere provides accurate active functional but not passive functional predictions for rabbit TA, EDL, and EDII muscles and call into question the need for more complex modeling assumptions often proposed.

Background Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. Methods Multifidus muscle biopsies were obtained from patients ( n  = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. Results Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI ( r  = -0.346, p  = 0.018, and r  = 0.386, p  = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area ( r  = 0.388, p  = 0.045). Conclusion Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Background Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology. Methods In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. Results No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. Conclusions The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.