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Computational modeling of damage in the hierarchical microstructure of skeletal muscles

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Abstract

One of the skeletal muscle’s exceptional properties is its high damage tolerance in terms of its high toughness, which allows the muscle to withstand cracks of millimeter length while maintaining most of its strength (Taylor et al., 2012). In skeletal muscles, damage occurs on different hierarchical levels of the microstructure. We analyze the damage behavior on hierarchy levels 3 (muscle fiber) and 4 (fascicle) on which the most common serious muscle injuries occur. Our model captures damage initiation and rupture of activated muscle fibers resulting from eccentric contractions. We consider the interaction between muscle fibers and endomysium and investigate the influence of the components titin and endomysium on the mechanical behavior in pre-damaged fascicles. Endomysium generally transmits contractile forces. Our results show that high strains in pre-damaged fiber regions are not transferred by the endomysium and, thus, adjacent undamaged fibers are well protected. Moreover, the results show titin’s extraordinary stabilization properties of pre-damaged muscle fibers, so that macroscopic strains of fascicles are hardly reduced in case of strongly pre-damaged fibers and intact titin.

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... At the submicron scale a sarcomere from the myofibril, its link to the endomysium, and the endomysium are shown. More specifically, several proteins actin, titin, myosin, troponin, tropomyosin, costameres, laminin, collagen IV, elastin and collagen I are represented] of parallel muscle fibers such as perfectly circular [46][47][48] (Fig. 2.C) or hexagonal [49,50] (Fig. 2.D). Perfectly circular arrangements are simple of use especially considering analytical homogenization methods, as these methods often consider elliptical or cylindrical fiber reinforced composites [51]. ...
... Usually, one macroscopic scale simulation is linked to several microscopic scale simulations. The hierarchical approach is implemented through the use of Finite Element Modeling for skeletal muscle homogenization [36,48,50,[55][56][57][58][59], mostly through the use of computational periodic homogenization [82] which requires the discretized microscopic scale geometry to be periodic in all space directions. Conversely, concurrent methods consider different scales simultaneously in different subvolumes of the same simulation and these scales may exchange information in hand-shake regions. ...
... Using Finite Element Modeling (FEM), Reproducing Kernel Particle Method (RKPM) [37], or analytical frameworks, muscle fibers are usually modeled by separate isotropic and anisotropic contributions. The isotropic behavior accounts for cellular components other than myofibrils and is usually represented by simple hyperelastic laws such as Neo-Hookean [47,48,50,55,56,60,76,87], second order Mooney Rivlin [58], Yeoh model [46,49], or a quadratic polynomial function [37]. ...
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Purpose: From the myofibrils to the whole muscle scale, muscle micro-constituents exhibit passive and active mechanical properties, potentially coupled to electrical, chemical, and thermal properties. Experimental characterization of some of these properties is currently not available for all muscle constituents. Multiscale multiphysics models have recently gained interest as a numerical alternative to investigate the healthy and diseased physiological behavior of the skeletal muscle. Methods: This paper refers to the multiscale mechanical models proposed in the literature to investigate the mechanical properties and behavior of skeletal muscles. More specifically, we focus on the scale transition methods, constitutive laws and experimental data implemented in these models. Results: Using scale transition methods such as homogenization, coupled to appropriate constitutive behavior of the constituents, these models explore the mechanisms of ageing, myopathies, sportive injuries, and muscle contraction. Conclusion: Emerging trends include the development of multiphysics simulations and the coupling of modeling with the acquisition of experimental data at different scales, with increasing focus to little known constituents such as the extracellular matrix and the protein titin.
... At the submicron scale a sarcomere from the myofibril, its link to the endomysium, and the endomysium are shown. More specifically, several proteins actin, titin, myosin, troponin, tropomyosin, costameres, laminin, collagen IV, elastin and collagen I are represented] of parallel muscle fibers such as perfectly circular [46][47][48] (Fig. 2.C) or hexagonal [49,50] (Fig. 2.D). Perfectly circular arrangements are simple of use especially considering analytical homogenization methods, as these methods often consider elliptical or cylindrical fiber reinforced composites [51]. ...
... Usually, one macroscopic scale simulation is linked to several microscopic scale simulations. The hierarchical approach is implemented through the use of Finite Element Modeling for skeletal muscle homogenization [36,48,50,[55][56][57][58][59], mostly through the use of computational periodic homogenization [82] which requires the discretized microscopic scale geometry to be periodic in all space directions. Conversely, concurrent methods consider different scales simultaneously in different subvolumes of the same simulation and these scales may exchange information in hand-shake regions. ...
... Using Finite Element Modeling (FEM), Reproducing Kernel Particle Method (RKPM) [37], or analytical frameworks, muscle fibers are usually modeled by separate isotropic and anisotropic contributions. The isotropic behavior accounts for cellular components other than myofibrils and is usually represented by simple hyperelastic laws such as Neo-Hookean [47,48,50,55,56,60,76,87], second order Mooney Rivlin [58], Yeoh model [46,49], or a quadratic polynomial function [37]. ...
Article
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Abstract Purpose : From the myofibrils to the whole muscle scale, muscle micro-constituents exhibit passive and active mechanical properties, potentially coupled to electrical, chemical, and thermal properties. Experimental characterization of some of these properties is currently not available for all muscle constituents. Multiscale multiphysics models have recently gained interest as a numerical alternative to investigate the healthy and diseased physiological behavior of the skeletal muscle. Methods : This paper refers to the multiscale mechanical models proposed in the literature to investigate the mechanical properties and behavior of skeletal muscles. More specifically, we focus on the scale transition methods, constitutive laws and experimental data implemented in these models. Results : Using scale transition methods such as homogenization, coupled to appropriate constitutive behavior of the constituents, these models explore the mechanisms of ageing, myopathies, sportive injuries, and muscle contraction. Conclusion : Emerging trends include the development of multiphysics simulations and the coupling of modeling with the acquisition of experimental data at different scales, with increasing focus to little known constituents such as the extracellular matrix and the protein titin.
... This question is very challenging to answer through experiments alone; however, computational modelling empowers us to precisely examine how microstructural variations contribute to macroscopic tissue properties. Previous micromechanical models generated from images of muscle cross-sections [21] and using Voronoi tessellation [22] examined how variation in muscle fibre and fascicle geometries influence tissue behaviour [21,23] and focused on cases such as damage [24] and ageing [25]. Micromechanical models that simulated changes in microstructure seen in DMD found that the effect of increased ECM area fraction was highly dependent on the stiffness of the ECM [26]. ...
... Micromechanical models that simulated changes in microstructure seen in DMD found that the effect of increased ECM area fraction was highly dependent on the stiffness of the ECM [26]. These models provided key insights but simplify the representation of the ECM as isotropic [24], transversely isotropic aligned with muscle fibres [21,26], or use a generalized helical assumption to represent collagen direction [22,23,25]. Therefore, they do not account for distinct ECM layers or incorporate the ability to examine the role of changes in collagen microstructure on muscle tissue properties. ...
... Therefore, they do not account for distinct ECM layers or incorporate the ability to examine the role of changes in collagen microstructure on muscle tissue properties. These models also rely on integrating measurements from several studies across different skeletal muscle groups [22][23][24][25], so it would be impossible to use these models to answer specific questions about variations in the structure and function of a particular muscle. ...
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Collagen accumulation is often used to characterize skeletal muscle fibrosis, but the role of collagen in passive muscle mechanics remains debated. Here we combined finite-element models and experiments to examine how collagen organization contributes to macroscopic muscle tissue properties. Tissue microstructure and mechanical properties were measured from in vitro biaxial experiments and imaging in dystrophin knockout (mdx) and wild-type (WT) diaphragm muscle. Micromechanical models of intramuscular and epimuscular extracellular matrix (ECM) regions were developed to account for complex microstructure and predict bulk properties, and directly calibrated and validated with the experiments. The models predicted that intramuscular collagen fibres align primarily in the cross-muscle fibre direction, with greater cross-muscle fibre alignment in mdx models compared with WT. Higher cross-muscle fibre stiffness was predicted in mdx models compared with WT models and differences between ECM and muscle properties were seen during cross-muscle fibre loading. Analysis of the models revealed that variation in collagen fibre distribution had a much more substantial impact on tissue stiffness than ECM area fraction. Taken together, we conclude that collagen organization explains anisotropic tissue properties observed in the diaphragm muscle and provides an explanation for the lack of correlation between collagen amount and tissue stiffness across experimental studies.
... 36 In particular, ST coupled with a distal compliant tendon, and given its parallel fiber arrangement, may lower the risk of muscle strain injuries. 5,8,37 On the contrary, the BF connected to a stiffer distal tendon and characterized by its pennated fiber orientation, is more susceptible to strain injuries, especially when subjected to high force and multiaxial loading conditions. 5,8,37 However, others have suggested that a reduction in tendon compliance could contribute to an increase in injury risk during sprinting, unless the changes in running posture enable the musculotendon complex to function at a shorter length. ...
... 5,8,37 On the contrary, the BF connected to a stiffer distal tendon and characterized by its pennated fiber orientation, is more susceptible to strain injuries, especially when subjected to high force and multiaxial loading conditions. 5,8,37 However, others have suggested that a reduction in tendon compliance could contribute to an increase in injury risk during sprinting, unless the changes in running posture enable the musculotendon complex to function at a shorter length. 6 Despite the similar morphological characteristics and tendon properties with the SM, the BFlh is more susceptible to injury due to greater changes in MTU length during sprinting. ...
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Tendon properties impact human locomotion, influencing sports performance, and injury prevention. Hamstrings play a crucial role in sprinting, particularly the biceps femoris long head (BFlh), which is prone to frequent injuries. It remains uncertain if BFlh exhibits distinct mechanical properties compared to other hamstring muscles. This study utilized free‐hand three‐dimensional ultrasound to assess morphological and mechanical properties of distal hamstrings tendons in 15 men. Scans were taken in prone position, with hip and knee extended, at rest and during 20%, 40%, 60%, and 80% of maximal voluntary isometric contraction of the knee flexors. Tendon length, volume, cross‐sectional area (CSA), and anteroposterior (AP) and mediolateral (ML) widths were quantified at three locations. Longitudinal and transverse deformations, stiffness, strain, and stress were estimated. The ST had the greatest tendon strain and the lowest stiffness as well as the highest CSA and AP and ML width strain compared to other tendons. Biceps femoris short head (BFsh) exhibited the least strain, AP and ML deformation. Further, BFlh displayed the highest stiffness and stress, and BFsh had the lowest stress. Additionally, deformation varied by region, with the proximal site showing generally the lowest CSA strain. Distal tendon mechanical properties differed among the hamstring muscles during isometric knee flexions. In contrast to other bi‐articular hamstrings, the BFlh high stiffness and stress may result in greater energy absorption by its muscle fascicles, rather than the distal tendon, during late swing in sprinting. This could partly account for the increased incidence of hamstring injuries in this muscle.
... Besides the basic modeling of physiologically realistic behavior of healthy skeletal muscle, the study of specific (pathological) biological processes is an ongoing research topic. Examples include models for damage [96], fatigue [18,19] and age-related loss of activation [97]. ...
Preprint
The shoulder joint is one of the functionally and anatomically most sophisticated articular systems in the human body. Both complex movement patterns and the stabilization of the highly mobile joint rely on intricate three-dimensional interactions among various components. Continuum-based finite element models can capture such complexity, and are thus particularly relevant in shoulder biomechanics. Considering their role as active joint stabilizers and force generators, skeletal muscles require special attention regarding their constitutive description. In this contribution, we propose a constitutive description to model active skeletal muscle within complex musculoskeletal systems, focusing on a novel continuum shoulder model. We thoroughly review existing material models before analyzing three selected ones in detail: an active-stress, an active-strain, and a generalized active-strain approach. To establish a basis for comparison, we identify the material parameters based on experimental stress-strain data obtained under various active and passive loading conditions. We discuss the concepts to incorporate active contractile behavior from a mathematical and physiological perspective, address analytical and numerical challenges arising from the mathematical formulations, and analyze the included biophysical principles of force generation in terms of physiological correctness and relevance for human shoulder modeling. Based on these insights, we present an improved constitutive model combining the studied models' most promising and relevant features. Using the example of a fusiform muscle, we investigate force generation, deformation, and kinematics during active isometric and free contractions. Eventually, we demonstrate the applicability of the suggested material model in a novel continuum mechanical model of the human shoulder.
... Different material models can be used for the models on each hierarchical level generated by the Python codes to model different physical processes on the microstructure, e.g. the chemoelectromechanical behavior during muscle fiber activation [15] or the damage behavior of muscle fibers [16]. ...
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Traditional robotic/mechatronic design has successfully exploited the attributes of heavy mechanical systems engineering, but future scientific trends suggest a need for technology that will emulate natural systems - biomimetic operation. This drive for new bio-mimetic principles is particularly prevalent in actuator design. This work will explore the design, using biomimetic principles, of actuators for the bipedal section of a humanoid robot. The paper will consider the design and selection of actuators and their incorporation into the legs of the humanoid. This will for the first stage of a humanoid standing 1.55m at the shoulder and weighing less than 25kg.
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This paper presents the authors' investigation results of applying the pneumatic artificial muscle actuation to above-knee prostheses. As a well-known muscle actuator, the pneumatic artificial muscle actuator features a number of unique advantages, including high power density, and similar elastic characteristics to biological muscles. Despite multiple applications in related areas, the application of pneumatic artificial muscle in above-knee prostheses has not been explored. Inspired by this fact, the research presented in this paper aims to develop a pneumatic artificial muscle-actuated above-knee prosthesis, with three specific objectives: (1) demonstrate the pneumatic artificial muscle actuation's capability in generating sufficient torque output to meet the locomotive requirements; (2) develop an effective control approach to enable the restoration of locomotive functions; (3) conduct preliminary testing of the prosthesis prototype on a healthy subject through a specially designed able-body adaptor. In the prosthesis design, an agonist-antagonist layout is utilized to obtain a bidirectional motion. To minimize the radial profile, an open-frame structure is used, with the purpose of allowing the expansion of the muscle actuators into the center space without interference. Also, the muscle actuator parameters are calculated to provide sufficient torque capacity (up to 140 N m) to meet the requirements of level walking. According to this design, the fabricated prototype weighs approximately 3 kg, with a range of motion of approximately 100 degrees. For the control of the prosthesis, a model-based torque control algorithm is developed based on the sliding mode control approach, which provides robust torque control for this highly nonlinear system. Combining this torque control algorithm with an impedance-based torque command generator (higher-level control algorithm), the fabricated prosthesis prototype has demonstrated a capability of providing a natural gait during treadmill walking experiments. [DOI: 10.1115/1.4004417]
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Data regarding direct athletic muscle injuries (caused by a direct blunt or sharp external force) compared to indirect ones (without the influence of a direct external trauma) are missing in the current literature-this distinction has clinical implications. To compare incidence, duration of absence and characteristics of indirect and direct anterior (quadriceps) and posterior thigh (hamstring) muscle injuries. 30 football teams and 1981 players were followed prospectively from 2001 until 2013. The team medical staff recorded individual player exposure and time-loss injuries. Muscle injuries were defined as indirect or direct according to their injury mechanism. In total, 2287 thigh muscle injuries were found, representing 25% of all injuries. Two thousand and three were valid for further analysis, of which 88% were indirect and 12% direct. The incidence was eight times higher for indirect injuries (1.48/1000 h) compared to direct muscle injuries (0.19/1000 h) (p<0.01). Indirect muscle injuries caused 19% of total absence, and direct injuries 1%. The mean lay-off time for indirect injuries amounted to 18.5 days and differed significantly from direct injuries which accounted for 7 days (p<0.001). 60% of indirect injuries and 76% of direct injuries occurred in match situations. Foul play was involved in 7% of all thigh muscle injuries, as well as in 2% of indirect injuries and 42% of direct injuries. Muscle anterior and posterior thigh injuries in elite football are more frequent than have been previously described. Direct injuries causing time loss are less frequent than indirect ones, and players can usually return to full activity in under half the average time for an indirect injury. Foul play is involved in 7.5% of all thigh muscle injuries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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The sliding filament theory of muscle contraction is widely accepted as the means by which muscles generate force during activation. Within the constraints of this theory, isometric, steady-state force produced during muscle activation is proportional to the amount of filament overlap. Previous studies from our laboratory demonstrated enhanced titin-based force in myofibrils that were actively stretched to lengths which exceeded filament overlap. This observation cannot be explained by the sliding filament theory. The aim of the present study was to further investigate the enhanced state of titin during active stretch. Specifically, we confirm that this enhanced state of force is observed in a mouse model and quantify the contribution of calcium to this force. Titin-based force was increased by up to four times that of passive force during active stretch of isolated myofibrils. Enhanced titin-based force has now been demonstrated in two distinct animal models, suggesting that modulation of titin-based force during active stretch is an inherent property of skeletal muscle. Our results also demonstrated that 15% of titin's enhanced state can be attributed to direct calcium effects on the protein, presumably a stiffening of the protein upon calcium binding to the E-rich region of the PEVK segment and selected Ig domain segments. We suggest that the remaining unexplained 85% of this extra force results from titin binding to the thin filament. With this enhanced force confirmed in the mouse model, future studies will aim to elucidate the proposed titin-thin filament interaction in actively stretched sarcomeres.
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An advanced shear lag model is developed to analyze the stress-shielding effect in injured muscle fiber by introducing the activation strain. The model considers three muscle fibers connected by the endomysium with the middle muscle fiber injured. Stress shielding describes the function of the lateral transmission of force in protecting the injured muscle fibers from being further injured by transferring force in the injured muscle fiber to its adjacent muscle fibers. Parameter studies demonstrate that the mechanical and geometrical properties of muscle fibers and the endomysium as well as the degree of injury can affect the stress-shielding effect. In conclusion, the model successfully demonstrates and captures, at least in a qualitative manner, the lateral transmission of force between an injured and a normal muscle fiber.
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Injuries to the quadriceps muscle of the thigh are frequent in sports and often the cause of serious and prolonged disability. Whether the injury is a contusion or strain of the muscle, the pathology and complications are the same. The most serious complication is myositis ossificans. A rationale of treatment is described based on a division of the injuries into four grades and measures appropriate to each degree are outlined. It is essential to restore normal muscle length as quickly as possible to decrease disability. (C)1969The American College of Sports Medicine
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Due to its high power-to-weight ratio, a pleated pneumatic artificial muscle (PPAM) offers an interesting alternative actuation source for robotic devices. Its inherent compliant behaviour excites another broad field of interest: assistive clinical devices such as powered exoskeletons and prosthetics. In this paper, the design of a pneumatically powered transtibial prosthetic device is presented. A first prototype has been built and provides a preliminary test bed for control algorithm development and testing with able-bodied subjects in laboratory conditions. The characteristics and working principle of a PPAM are described. The design specifications and the mechanical model of the prosthesis are discussed. The mechanical design and the control structure are outlined. Furthermore, some initial walking trials with an able-bodied subject wearing the prosthesis prototype are presented and discussed.
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In this paper we present a fully three-dimensional finite-strain damage model for fibrous soft tissue. Continuum damage mechanics is used to describe the softening behaviour of soft tissues under large deformation. The structural model is formulated using the concept of internal variables that provides a very general description of materials involving irreversible effects. We considered the internal variables associated to damage to correspond to separated contributions of the matrix and fibres. In order to show clearly the performance of the constitutive model, we present 3D simulations of the behaviour of the human medial collateral ligament and of a coronary artery. Results show that the model is able to capture the typical stress–strain behaviour observed in fibrous soft tissues and seems to confirm the soundness of the proposed formulation. Copyright © 2006 John Wiley & Sons, Ltd.
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Bone cutting is an essential part of orthopaedic surgery when bone is fractured or damaged by a disease and is used for pins insertion and plates fixation. A finite element model of bone cutting is developed and compared with experimental results. The model allows the interaction between the bone and cutting tool to be studied, hence enabling the evaluation and optimization of the cutting procedure. Results of finite element simulations are obtained for the cutting force as a function of cutting parameters. A strong dependence of cutting parameters on the cutting force was found and described in this paper.
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A fully three-dimensional finite-strain viscoelastic model is developed, characterized by: (i) general anisotropic response, (ii) uncoupled bulk and deviatoric response over any range of deformations, (iii) general relaxation functions, and (iv) recovery of finite elasticity for very fast or very slow processes; in particular, classical models of rubber elasticity (e.g. Mooney-Rivlin). Continuum damage mechanics is employed to develop a simple isotropic damage mechanism, which incorporates softening behavior under deformation, and leads to progressive degradation of the storage modulus in a cyclic test with increasing amplitude (Mullins' effect). A numerical integration procedure is proposed which trivially satisfies objectivity and bypasses the use of midpoint configurations. The resulting algorithm can be exactly linearized in closed form, and leads to symmetric tangent moduli. Quasi-incompressible response is accounted for within the context of a three-field variational formulation of the Hu-Washizu type.
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Fracture toughness is important for any material, but to date there have been few investigations of this mechanical property in soft mammalian tissues. This paper presents new data on porcine muscle tissue and a detailed analysis of all previous work. The conclusion is that, in most cases, fracture toughness has not in fact been measured for these tissues. Reanalysis of the previous work shows that failure of the test specimens generally occurred at the material's ultimate strength, implying that no information about toughness can be obtained from the results. This finding applied to work on cartilage, artificial neocartilage, muscle and the TMJ disc. Our own data, which was also found to be invalid, gave measured fracture toughness values which were highly variable and showed a strong dependence on the crack growth increment. The net-section failure stress and failure energy were relatively constant in large specimens, independent of crack length, whilst for smaller specimens they showed a strong size effect. These findings are explained by the fact that the process zone size, estimated here using the critical distance parameter L, was similar to, or larger than, critical specimen dimensions (crack length and specimen width). Whilst this analysis casts doubt on much of the published literature, a useful finding is that soft tissues are highly tolerant of defects, able to withstand the presence of cracks several millimetres in length without significant loss of strength.
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HERZOG, W., M. DUVALL, and T. R. LEONARD. Molecular mechanisms of muscle force regulation: a role for titin? Exerc. Sport Sci. Rev., Vol. 40, No. 1, pp. 50-57, 2012. Muscle contraction and force regulation is thought to occur exclusively through the interaction of the contractile proteins actin and myosin and in accordance with the assumptions underlying the cross-bridge theory. Here, we demonstrate that a third protein, titin, plays a major role in muscle force regulation, particularly for eccentric contractions and at long muscle and sarcomere lengths.
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The aim of this study was to analyse the mechanisms that determine why small groups of muscle fibres may have different mechanical properties than single muscle fibres. The method used combined light microscopy and tensile testing on single fibres and small groups of fibres from raw and cooked (80 °C) meat, from both conditioned and unconditioned porcine longissimus muscle. The results showed that small groups of fibres had different breaking properties than constituent single fibres in raw muscle, but that these differences diminished on cooking. Raw groups of fibres showed a more uniform lengthening along their entire length and a higher extension to rupture than single fibres. Conditioning increased maximum strains in both single fibres and small fibre groups. In unconditioned cooked meat, single fibres and fibre groups showed comparable breaking stresses and extensions. Conditioning resulted in a lower strength in fibre groups than in single fibres. These results show that (endomysial) connective tissue linkages between adjacent muscle fibres in a small group significantly alter the breaking behaviour of single fibres. The effects of these connective tissue linkages are not reduced by conditioning alone, but are largely diminished by cooking to 80 °C.
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Finite element models (FEM) dedicated to vertebral fracture simulations rarely take into account the rate dependency of the bone material properties due to limited available data. This study aims to calibrate the mechanical properties of a vertebral body FEM using an inverse method based on experiments performed at slow and fast dynamic loading conditions. A detailed FEM of a human lumbar vertebral body (23,394 elements) was developed and tested under compression at 2,500 and 10 mm s⁻¹. A central composite design was used to adjust the mechanical properties (Young modulus, yield stress, and yield strain) while optimizing four criteria (ultimate strain and stress of cortical and trabecular bone) until the failure load and energy at failure reached experimental results from the literature. At 2,500 mm s⁻¹, results from the calibrated simulation were in good agreement with the average experimental data (1.5% difference for the failure load and 0.1% for the energy). At 10 mm s⁻¹, they were in good agreement with the average experimental failure load (0.6% difference), and within one standard deviation of the reported range of energy to failure. The proposed method provides a relevant mean to identify the mechanical properties of the vertebral body in dynamic loadings.
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The goal of this work was to create a finite element micromechanical model of the myotendinous junction (MTJ) to examine how the structure and mechanics of the MTJ affect the local micro-scale strains experienced by muscle fibers. We validated the model through comparisons with histological longitudinal sections of muscles fixed in slack and stretched positions. The model predicted deformations of the A-bands within the fiber near the MTJ that were similar to those measured from the histological sections. We then used the model to predict the dependence of local fiber strains on activation and the mechanical properties of the endomysium. The model predicted that peak micro-scale strains increase with activation and as the compliance of the endomysium decreases. Analysis of the models revealed that, in passive stretch, local fiber strains are governed by the difference of the mechanical properties between the fibers and the endomysium. In active stretch, strain distributions are governed by the difference in cross-sectional area along the length of the tapered region of the fiber near the MTJ. The endomysium provides passive resistance that balances the active forces and prevents the tapered region of the fiber from undergoing excessive strain. These model predictions lead to the following hypotheses: (i) the increased likelihood of injury during active lengthening of muscle fibers may be due to the increase in peak strain with activation and (ii) endomysium may play a role in protecting fibers from injury by reducing the strains within the fiber at the MTJ.
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The importance of the extracellular matrix (ECM) in muscle is widely recognized, since ECM plays a central role in proper muscle development (Buck and Horwitz, 1987), tissue structural support (Purslow, 2002), and transmission of mechanical signals between fibers and tendon (Huijing, 1999). Since substrate biomechanical properties have been shown to be critical in the biology of tissue development and remodeling (Engler et al., 2006; Gilbert et al., 2010), it is likely that mechanics are critical for ECM to perform its function. Unfortunately, there are almost no data available regarding skeletal muscle ECM viscoelastic properties. This is primarily due to the impossibility of isolating and testing muscle ECM. Therefore, this note presents a new method to quantify viscoelastic ECM modulus by combining tests of single muscle fibers and fiber bundles. Our results demonstrate that ECM is a highly nonlinearly elastic material, while muscle fibers are linearly elastic.
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Peak Ca(2+)-activated specific force (force/fiber cross-sectional area) of human chemically skinned vastus lateralis muscle fiber segments was determined before and after a fixed-end contraction or an eccentric contraction of standardized magnitude (+0.25 optimal fiber length) and velocity (0.50 unloaded shortening velocity). Fiber myosin heavy chain (MHC) isoform content was assayed by SDS-PAGE. Posteccentric force deficit, a marker of damage, was similar for type I and IIa fibers but threefold greater for type IIa/IIx hybrid fibers. A fixed-end contraction had no significant effect on force. Multiple linear regression revealed that posteccentric force was explained by a model consisting of a fiber type-independent and a fiber type-specific component (r(2) = 0.91). Preeccentric specific force was directly associated with a greater posteccentric force deficit. When preeccentric force was held constant, type I and IIa fibers showed identical susceptibility to damage, while type IIa/IIx fibers showed a significantly greater force loss. This heightened sensitivity to damage was directly related to the amount of type IIx MHC in the hybrid fiber. Our model reveals a fiber-type sensitivity of the myofilament lattice or cytoskeleton to mechanical strain that can be described as follows: type IIa/IIx > type IIa = type I. If these properties extend to fibers in vivo, then alterations in the number of type IIa/IIx fibers may modify a muscle's susceptibility to eccentric damage.
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The giant muscle protein titin, the "backbone" of the sarcomere, harbors a complex molecular spring whose stiffness is variably tuned in health and disease. Titin is increasingly recognized as a crucial integrator of diverse myocyte signaling pathways. The titin-associated signalosome includes hotspots of protein-protein interactions important for the regulation of protein quality-control mechanisms, hypertrophic gene activation, and mechanosensing.
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Post-translational modifications, along with isoform splicing, of titin determine the passive tension development of stretched sarcomeres. It was recently shown that PKCalpha phosphorylates two highly-conserved residues (S26 and S170) of the PEVK region in cardiac titin, resulting in passive tension increase. To determine how each phosphorylated residue affects myocardial stiffness, we generated three recombinant mutant PEVK fragments (S26A, S170A and S170A/S26A), each flanked by Ig domains. Single-molecule force spectroscopy shows that PKCalpha decreases the PEVK persistence length (from 0.99 to 0.68 nm); the majority of this decrease is attributable to phosphorylation of S26. Before PKCalpha, all three mutant PEVK fragments showed at least 40% decrease in persistence length compared to wildtype. Furthermore, Ig domain unfolding force measurements indicate that PEVK's flanking Ig domains are relatively unstable compared to other titin Ig domains. We conclude that phosphorylation of S26 is the primary mechanism through which PKCalpha modulates cardiac stiffness.
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The purpose of this study is to develop a constitutive model of skeletal muscle that describes material anisotropy, viscoelasticity and damage of muscle tissue. A free energy function is described as the sum of volumetric elastic, isochoric elastic and isochoric viscoelastic parts. The isochoric elastic part is divided into two types of shear response and the response in the fiber direction. To represent the dependence of the mechanical properties on muscle activity, we incorporate a contractile element into the model. The viscoelasticity of muscle is modeled as a three-dimensional model constructed by extending the one-dimensional generalized Maxwell model. Based on the framework of continuum damage mechanics, the anisotropic damage of muscle tissue is expressed by a second-order damage tensor. The evolution of the damage is assumed to depend on the current strain and damage. The evolution equation is formulated using the representation theorem of tensor functions. The proposed model is applied to the experimental data on tensile mechanical properties in the fiber direction and the compression properties in the fiber and cross-fiber directions in literature. The model can predict non-linear mechanical properties and breaking points.
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Skeletal muscle is composed of two primary structural components, contractile myofibrils and extracellular matrix (ECM). The myofibrils adhere to the surrounding endomysium through the basal lamina, sarcolemma and dystrophin, and dystrophin associated glycoprotein (DAG). In this study, a novel shear lag type model is developed to investigate the mechanics of injury to the single muscle fiber due to lengthening contractions. A single muscle fiber is considered as a composite system with reinforced by the contractile myofibrils. The lateral linkages between myofibril and endomysium is modeled as a zero thickness coating layer, that could be injured under high interfacial shear stress. The results shows that the degree of the muscle injury is correlated to the magnitude of the passive stretch during the contraction. Dystrophic muscles are more susceptible to contraction induced injury due to lack of DAG complex in lateral linkage.
Article
Many skeletal muscles, including the feline biceps femoris, are composed of short, tapered myofibers arranged in an overlapping longitudinal series. The endomysium of such muscles transfers tension between overlapping myofibers, and is thus an elastic element in series with them. The endomysium of the cat biceps femoris contains curvilinear collagen fibrils in an approximately isotropic (random) array. The collagen fibrils undergo only a modest reorientation as the myofibers shorten or lengthen within the physiological range. A geometrical model predicts no change in the thickness of the endomysium on changing muscle fiber length and quantifies the expected collagen fibril reorientation in the endomysium as a function of muscle extension. It is also demonstrated that a high proportion of the collagen fibrils will be curvilinear at all sarcomere lengths. The organization of endomysial collagen is appropriate for the transfer of loads between myofibers by means of shear.