It is widely accepted that the myotendinous junction is the main site for transmission of the force generated within the sarcomeres onto the bone (12). Therefore, to facilitate controlled bodily motion, the importance of myotendinous force transmission is clear. Conceivably, owing to that, the classical point of view regards the myotendinous junction as the exclusive channel for force transmission. This has consequences in determining the understanding of muscular mechanics:
- (I) Intramuscularly: Mechanical connections between the muscle fibers and the extracellular matrix are considered to exist solely at the ends of the fiber. Consequently, muscle fibers are considered as units functioning independently of each other.
- (II) Epimuscularly: In classical muscle mechanics experiments performed to determine muscle isometric length-force characteristics and dynamic characteristics, muscle force is measured in the following conditions: (i) the targeted muscle is fully dissected except for its innervation and blood supply, and (ii) muscle force is measured at one tendon exclusively. In such an approach, the mechanical connections between the muscle belly and its surroundings are considered to be facilitated solely via the myotendinous junctions. As a consequence, the following idealizations that actually possess the same mechanical meaning have been made: (i) the muscle studied in situ is considered as "fully isolated" from its surroundings, (ii) the muscle force exerted at the tendon from which measurements are taken is considered implicitly to be equal to the force exerted at the other tendon, and (iii) determined length-force characteristics are considered unique properties of the specific target muscle. These idealizations have become the established principles of skeletal muscle mechanics and have led to the consideration of muscles as independent functional units.
However, in addition to the myotendinous junctions, muscle fibers and intramuscular connective tissue stroma are connected to each other along the full length of the muscle fibers. Adjacent myofibrils are connected, and trans-sarcolemmal molecules connect the cytoskeleton to laminin, which is connected to the basal lamina (for a review, see (2)). The basal lamina, in turn, is connected to the endomysium (Fig. 1A) that forms a three-dimensional structure of tunnels within which the muscle fibers are operating (Fig. 1B). These structures have been shown to transmit muscle force (4,10,15): intramuscular myofascial force transmission.
Moreover, within the context of its intact connective tissue surroundings (the in vivo condition), muscle is not an isolated and independent entity. Instead, collagenous linkages between epimysia of adjacent muscles provide direct intermuscular connections, and structures such as the neurovascular tracts provide indirect intermuscular connections. In addition, compartmental boundaries (e.g., intermuscular septa, interosseal membranes, periost, and compartmental fascia) are continuous with neurovascular tracts. Such extramuscular connections bind muscular and nonmuscular tissues at several locations, in addition to the tendon origins and insertions. Our research groups have shown that substantial amounts of muscle force can be transmitted via this integral system of connections: epimuscular myofascial force transmission (18).
The goal of this paper is to review the key aspects, determinants, and effects of this novel concept and to indicate its wide range of possible implications for muscle function in health and disease.
UNEQUAL PROXIMAL AND DISTAL FORCES: THE CHARACTERISTIC EFFECT
Epimuscular myofascial force transmission has major effects on muscular mechanics. Assessment of these effects requires experiments that are designed differently than typical studies. In recent experiments performed for that specific purpose, (i) the muscle belly was not dissected (i.e., its epimuscular connections were left intact), and (ii) instead of measuring the force exerted at only one tendon, the forces exerted at both proximal and distal tendons were measured simultaneously (Fig. 2A). This approach showed the characteristic effect of epimuscular myofascial force transmission on muscle length-force characteristics: proximo-distal force differences (e.g., (17)). The experiments discussed here involve length changes of a target muscle and differences in proximo-distal forces as a function of muscle length. For example, it has been shown for the rat extensor digitorum longus (EDL) muscle, with extramuscular connections exclusively (i.e., after removal of its synergistic muscles), that increasing muscle length distally caused an increase in proximo-distal force differences (Fig. 2B) of up to 40% of the proximal force (16).
It should be noted that even in experiments performed on fully dissected muscle, the blood supply and innervations were kept intact as much as possible, to sustain the physiological state. Accordingly, specific parts of the neurovascular tract, usually proximally located with respect to the muscle, were always left intact. These remaining extramuscular connections were shown to be transmitting muscle force, leading to notable proximo-distal force differences (16). Therefore, even the fully dissected experimental muscle in situ cannot be considered to be truly isolated mechanically from its surroundings. Despite that, such assumptions have typically governed earlier experimental work, or conditions that yield minimal net extramuscular myofascial effects may have been selected almost intuitively.
Above all, proximo-distal force differences provide clear evidence for the existence of a potentially important pathway for force transmission additional to the myotendinous pathway. Moreover, because of epimuscular myofascial force transmission, muscles may be viewed as having additional origins and/or insertions because part of the muscular force is transmitted from the muscle to other muscles or nonmuscular structures.
MUSCLE RELATIVE POSITION: A MAJOR DETERMINANT OF MUSCLE FORCE
For muscles with intact epimuscular connections, changes in muscle length cause changes in position of the muscle relative to its neighboring muscles and nonmuscular structures. Recent experiments showed remarkable results caused by muscle lengthening. Huijing and Baan (5) reported proximo-distal force differences in the rat EDL such that the isometric forces exerted at the tendon that was pulled to impose the length changes was higher. However, despite equal proximal and distal muscle lengthening, the proximo-distal force differences were not the same. Therefore, different length-force curves were obtained for the same muscle as a result of different relative positions. Thus, in addition to muscle length, muscle relative position is a major determinant of muscle force. These results were supported by other studies that showed that fixing the muscle-tendon complex length of the target muscle, but changing its relative position (8,19), caused the following: (i) unequal proximal and distal muscle forces for most positions and (ii) increased proximo-distal force differences with increasing relative distance of the muscle from a reference position.
It is important to introduce the concept of epimuscular myofascial loads at this point; the proximo-distal force differences at each muscle length represent the resultant of such forces originating from stretching epimuscular connections. These epimuscular connections feature complex mechanics: (i) similar to other connective tissue structures (11), they are thought to have nonlinear force-deformation characteristics, (ii) their mechanical properties are inhomogeneous (e.g., the proximal parts of neurovascular tracts are stiffer than the distal parts (16)), and (iii) they are prestrained (18). Therefore, epimuscular myofascial loads are expected to be distributed heterogeneously over the muscle belly and may vary as a function of muscle relative position. Consequently, even for lengths at which the proximo-distal force difference is close to zero, it is thought that the resultant force is zero but not the local forces along the muscle.
Recall now the typical approach which considers the muscle fiber as comprised of sarcomeres arranged in series, loaded axially and at the ends, exclusively. Such conditions require that the force on each of the serially arranged element is identical to the force exerted at the proximal and distal ends (Fig. 3A). As a consequence, the length of a sarcomere is accepted to be determined exclusively by its interaction with sarcomeres arranged in series and within the same fiber. However, because of epimuscular myofascial force transmission, this consideration may be mechanically incomplete. The force balance determining the length of a sarcomere is much more involved (Fig. 3B); it should include epimuscular myofascial loads. Moreover, taking into account the continuous mechanism of epimuscular and intramuscular myofascial force transmission, such force balance also should include the forces exerted by the extracellular matrix and the forces of the sarcomeres located in the neighboring muscle fibers (i.e., intramuscular myofascial loads).
Changes in the relative position of a muscle are thought to be the key mechanism responsible for the effects of epimuscular myofascial force transmission. (i) As the length of the target muscle increases, the collagenous intermuscular connections between the extracellular matrices of adjacent muscles are stretched. This will increase the myofascial loads on the connective tissue stroma. Differences in moment arms and the number of joints spanned by different muscles may cause differential length changes and therefore relative position changes of neighboring muscles. (ii) Upon any length change, the position of a muscle with respect to the fixed bony structures of the musculoskeletal system changes, thereby causing stretching of all epimuscular connections, including neurovascular tracts and compartmental boundaries, thus causing myofascial loads to build up.
EFFECTS OF MYOFASCIAL LOADS: MAJOR SARCOMERE LENGTH HETEROGENEITY
A free body diagram for a hypothetical muscle fiber within a muscle in the context of fascial integrity implies that myofascial loads may cause sarcomere length heterogeneity (Fig. 3B). Although sarcomere length distributions need to be studied experimentally, this is difficult as the target muscle is surrounded by compartmental connective tissues and other muscles, which obscure the view to the sarcomeres. On the other hand, if one gains access to a muscle, the myofascial force transmission mechanism may become disrupted, which defeats the purpose of the experiment. However, finite element modeling, taking into account the peripheral connections between muscle fibers and extracellular matrix (Fig. 4A) and the muscle's extramuscular connections (Fig. 4B), allows for studying the effects of such force transmission on sarcomere length distributions (e.g., (15,17,19)). The fiber direction strain within the model represents a measure of normalized change of length and reflects the lengthening (positive strain) or shortening (negative strain) from an initial reference configuration (usually at optimum length). Although the model does not contain morphological representations of sarcomeres, the local strains constitute estimates of local sarcomere lengths.
Figure 5 exemplifies the detailed results of such modeling, showing the fiber direction strain distributions within a fascicle (marked in Fig. 4B) that was studied in isolation and within the muscle. The modeling procedure included the following steps: (i) the whole muscle model with extramuscular connections was activated maximally and stretched such that the target fascicle was lengthened by 9%; (ii) nodal displacements of the proximal and distal ends of the target fascicle were obtained; (iii) the target fascicle was isolated, maximally activated, and its ends were brought to the exact locations achieved by the same fascicle within the muscle. In the isolated fascicle condition, mechanical interactions between the fiber and extracellular matrix were possible; however, myofascial loads from the interaction with neighboring fascicles and stretching of extramuscular connections were not accounted for. The isolated fascicle shows a nearly homogeneous strain distribution (Fig. 5A), whereas strains in the intact fascicle were much smaller at the proximal than the distal end (Fig. 5B). A remarkable result was that despite the great length of the fascicle (longer than optimal length), the proximal sections of the fascicle shortened by up to 8%, whereas the distal sections were stretched by up to 24%. These results show that epimuscular myofascial force transmission may cause a major serial sarcomere length heterogeneity.
In contrast with traditional approaches, this has important implications. Julian and Morgan (7) argued that intersarcomere dynamics limits the lengths of all sarcomeres to the descending limb of the length-force curve for muscles at lengths greater than the optimum length. In contrast, classical models of instability (1,25) showed, for an isolated fiber undergoing fixed end contraction, that only one sarcomere can ever reside on the descending limb of the force-length relationship. The results obtained for the fascicle modeled under the action of myofascial loads challenge the concept of sarcomere length distribution being predominantly limited to the ascending or descending limb of the length-force curve and show that these distributions may range from the domains of the ascending limb to the descending limb of their sarcomere length-force curves. Such results also suggest that within the context of surrounding muscles and connective tissues, distributions of sarcomere length should be expected as physiological phenomena.
On the other hand, studying the fiber direction strains showed that, in addition to a serial distribution of sarcomere lengths, myofascial force transmission also leads to a parallel distribution of sarcomere lengths, that is, heterogeneity of mean sarcomere lengths across different fibers (8,17). In Figure 6, the mean fiber direction strain distributions for different fascicles are shown for the medial (with extramuscular connections) and lateral (with intermuscular connections) faces of the rat EDL modeled with intact epimuscular connections. The nodes along the length of myofiber elements represent fascicle groups (numbered from 1 to 7, Fig. 6A). The mean fiber strain values for the medial and lateral faces of the rat EDL are different for all fascicles, indicating a substantial parallel distribution of sarcomere length (Fig. 6B). Moreover, the differences in the mean fiber direction strain distribution between the lateral and medial faces are an additional indication for a parallel distribution of sarcomere lengths.
MUSCLE LENGTH-FORCE CHARACTERISTICS ARE NOT UNIQUE PROPERTIES OF INDIVIDUAL MUSCLES
The major determinants of muscle length-force characteristics are muscle optimal force (the maximum isometric force exerted by an active muscle), muscle optimum length (the length at which the muscle exerts its maximal active isometric force), and muscle active slack length (the shortest length at which the muscle can still exert nonzero force). Maximal active isometric force often is taken as an indication of a muscle's capacity for force production, and the range from active slack length to optimal length is taken as an indicator of movement capability with active force exertion within the potential range of motion of a certain joint. However, in pathological conditions such as spastic contractures, compromised length range of active force exertion may impose a limitation to joint range of motion before being limited by ligaments or bony constraints.
Recent experiments have shown that the above-mentioned determinants of the length-force characteristics of a muscle may differ substantially, depending on if the synergistic muscles are removed or left intact because of myofascial force transmission (e.g., (17)). For rat EDL, the magnitude of the proximo-distal force differences were much higher, the range of active force exertion was increased substantially, and the distal optimal force was significantly higher with the synergistic muscles intact compared with when they were removed.
In earlier experiments on isolated muscle, serial (14) and parallel sarcomere length distributions (13) were shown to enhance active muscle excursion. In agreement with these findings, the more pronounced serial and parallel heterogeneity of sarcomere lengths shown using finite element modeling for EDL with epimuscular connections (17) explains the increased active excursion. However, for isolated muscle, maximal active isometric force is decreased (3). Therefore, the high distal maximal force of the rat EDL with its synergists intact cannot be ascribable solely to the force generated within its sarcomeres. The additional force comes from its synergistic muscles via myofascial pathways.
Experimental manipulation of the components of epimuscular myofascial force transmission also caused changes in the shape of the muscle length-force curve (9,18). For example, the extensor hallucis longus muscle had different length-force characteristics with EDL present or removed (18).
We conclude from the results summarized above that the forces exerted at the origins and insertions of muscles change as a function of muscle length and the mechanical conditions in which the muscle is functioning. Therefore, because of epimuscular myofascial force transmission, length-force characteristics of muscles depend on the conditions within which the muscle functions and hence are not fixed properties of a specific muscle.
Epimuscular myofascial force transmission has been shown to occur between antagonistic muscles of the lower leg (24). Distal length changes of the deep flexor muscles affect the forces of its antagonistic muscles restrained at constant length. The variable proximo-distal force differences indicated net proximally directed epimuscular myofascial loads on EDL at short deep flexor lengths and net distally directed loads at long deep flexor lengths. Forces of other anterior crural muscles (i.e., tibialis anterior and extensor hallucis longus) and the peroneal muscles decreased by as much as 50%. Thus, epimuscular myofascial force transmission is expected to have several important implications.
We showed that the magnitude of force exerted and the determinants of the length-force characteristics were strongly affected by myofascial force transmission. These are some of the key parameters orthopedists aim at controlling in treating spastic contractures. Therefore, knowledge of myofascial force transmission and its effect on muscle properties is clinically relevant when planning and performing surgeries aimed at restoring normal range of motion and functionality in patients with spasticity. Spasticity and muscle contractures, as they occur after stroke or in patients with cerebral palsy, often limit the range of muscle and joint excursion. Surgical treatment of such movement restrictions may involve cutting the intramuscular aponeurosis longitudinally. The goal of such "aponeurotomies" is to increase a muscle's active range of excursion and to weaken the muscle if there is a perceived force imbalance with the antagonistic muscles. Intramuscular and epimuscular myofascial force transmissions play a crucial role in determining the acute effects of such surgical interventions. For example, interfering with the myotendinous force transmission alone, that is, creating a discontinuity in the aponeurosis exclusively was shown to have no notable effect on force and length-force characteristics (21). Only after creating an additional discontinuity in the muscles' extracellular matrix, the desired acute effects of reduced force and increased active range of excursion were achieved. The increased excursion can primarily be explained by an increase in sarcomere length heterogeneity predominantly in muscle fibers located proximal to the intervention, whereas the muscle weakening is primarily caused by a zone of very short sarcomeres in fibers distal to the intervention (21). Because of epimuscular myofascial force transmission, the acute effects of surgical intervention were not unique but were dependent on some associated mechanical conditions (20,22). Such increased understanding of the effects of aponeurotomies allowed us to optimize the location of intervention to maximize the desired outcomes (23). Another effect of aponeurotomy due to epimuscular myofascial force transmission is the weakening of not only the target muscle but also its nontargeted synergists (17). Note that the proximo-distal force differences are indicative of differential mechanical effects at the muscle's origin and insertion site. For poly-articular muscles, this has special functional consequences because such differential effects manifest themselves differently at the joints spanned by the target muscle (22). For that reason, when attempting to correct a functional problem at a distal joint, the surgery is likely to alter the mechanics at the proximal joint, as well. Therefore, it seems important to take into account the role of epimuscular myofascial force transmission in designing surgical interventions so as to not cause a desired effect at the target joint but a highly unfavorable effect at nontargeted joints that are spanned by the muscle.
Epimuscular myofascial force transmission has major effects on muscular mechanics. We expect that improving our understanding of myofascial force transmission may allow for the development of new and effective approaches to treat muscle injuries and diseases, such as muscular dystrophies, repetitive strain injury, and spasticity. We further venture that proper understanding of myofascial force transmission also may lead to new and more effective reconstructive techniques. The effects of myofascial force transmission during muscular activity in vivo need to be determined. Recent data obtained on in vivo muscle function using magnetic resonance imaging showed that myofascial force transmission can cause major sarcomere length heterogeneity in human lower leg muscles. These preliminary findings provide strong support for the importance of myofascial force transmission in vivo and indicate the need for studies to further explore the effects and implications of these force transmission pathways (6).
The author acknowledges Peter Huijing, Guus Baan, Huub Maas, Bart Koopman, and Henk Grootenboer who coauthored the papers that parts of this work are based on. The author also would like to thank Richard Jaspers, Ahu Türkoğlu Filiz Ateş, Alper Yaman, and Cengizhan Öztürk for help in generating some of the modeling and experimentally based ideas and approaches described here.
Different parts of this work were supported by the following: (i) The Turkish Academy of Sciences (TÜBA) under the Distinguished Young Scientist Award; (ii) Boğaziçi University Research Fund under grants 04HX102 and 09HX101D; (iii) The Scientific and Technological Research Council of Turkey (TÜBI˙TAK) under grants 105S483 and 108M431 to Can A. Yucesoy; (iv) the Vrije Universiteit, Amsterdam; and (v) the Universiteit Twente, Enschede.
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