Muscle as a collagen fiber reinforced composite: a review of force transmission in muscle and whole limb

Even though no direct physiologic evidence proving that myo-tendinous junctions at the end of myofibers are sites of force transmission is available, these locations are accepted to support this function, because its specialized morphology resembles that of load-bearing membranes in structure and location: Its design is fit for force transmission of force exerted by myofibers to tendinous fibrous material. Shearing of the interface between these structures is thought to be stronger than direct tensile transmission. On the basis of morphological studies of 'in-series fibered muscle' and biomechanical modeling it has been argued previously that force could also be transmitted laterally from the tapered ends of myofibers onto in series myofiber via the intramuscular connective tissue component. Shearing of the interfaces between myofibers is hypothesized to be the mechanisms of transmission. The interfaces are made up of basal membranes of both myofibers and their common endomysium. The issue of lateral force transmission from myofibers has not been addressed for whole muscle, in which myofibers are attached at both ends to tendinous aponeuroses, nor is any direct experimental evidence available about possible functional importance of this phenomenon in whole muscle. The primary objective of this presentation is to review available literature on myo-tendinous and myo-fascial force transmission, present evidence from experiments involving tenotomy, fasciatomy and aponeurotomy regarding its importance and consider implications for our thinking about muscle(s) and movement.     

Understanding the basic biology underlying the flavor world of children

Health organizations worldwide recommend that adults and children minimize intakes of excess energy and salty, sweet, and fatty foods (all of which are highly preferred tastes) and eat diets richer in whole grains, low- and non- fat dairy products, legumes, fish, lean meat, fruits, and vegetables (many of which taste bitter). Despite such recommendations and the well-established benefits of these foods to human health, adults are not complying, nor are their children. A primary reason for this difficulty is...     

Deformation and three-dimensional displacement of fibers in isometrically contracting rat plantaris muscles

In this study, the deformation of different fibers of the rat m. plantaris during "isometric" contractions at different muscle lengths was considered. Because the m. plantaris has an obviously inhomogeneous architecture, its fibers on the medial side of the muscle belly are judged to be shorter than those on the lateral side of it. It was expected that longitudinal deformation of different fibers would vary accordingly. A 3D video analysis of contracting muscle showed that longitudinal strain of fibers as a function of muscle length does not differ between fibers on different sides of the muscle. Apart from longitudinal shortening, the fibers were also displaced laterally during a contraction. The fibers displaced during a contraction in a direction perpendicular to their longitudinal axis. The displacement of the fibers occurred asymmetrically, resulting in a helical deformation of the whole muscle. It is concluded that the asymmetric displacement and the helical deformation must result from transversal forces between the fibers. It is hypothesized that these transversal forces cancel out differences in longitudinal strains that might exist between fibers.     

Effects of inter- and extramuscular myofascial force transmission on adjacent synergistic muscles: assessment by experiments and finite-element modeling

The effects of inter- and extramuscular myofascial force transmission on muscle length force characteristics were studied in rat. Connective tissues at the bellies of the experimental synergistic muscles of the anterior crural compartment were left intact. Extensor digitorium longus (EDL) muscle was lengthened distally whereas tibialis anterior (TA) and extensor hallucis longus (EHL) were kept at constant muscle–tendon complex length. Substantial differences were found in EDL force measured at the proximal and distal tendons (maximally 46% of the proximal force). EDL with intact inter- as well as extramuscular connections had an increased length range between active slack and optimum length compared to EDL with extramuscular connections exclusively: optimum muscle length was shifted by more than 2 mm. Distal EDL lengthening caused the distal force exerted by TA+EHL complex to decrease (approximately 17% of the initial force). This indicates increased intermuscular myofascial force transmission from TA+EHL muscle complex to EDL muscle.

Finite-element modeling showed that: (1) Inter- and extramuscular myofascial force transmission leads to a substantial distribution of the lengths of the sarcomeres arranged in series within muscle fibers. Distribution of stress within the muscle fibers showed that the muscle fiber cannot be considered as a unit exerting equal forces at both ends. (2) Increased heterogeneity of mean fiber sarcomere lengths (i.e., a “parallel” distribution of length of sarcomeres among different muscle fibers) is found, particularly at high muscle lengths. This also explains the shift in muscle optimum length to higher lengths.

It is concluded that inter- and extramuscular myofascial force transmission has substantial effects on muscle length–force characteristics.     

CD134 as target for specific drug delivery to auto-aggressive CD4<Superscript>+</Superscript>T cells in adjuvant arthritis

T cells have an important role during the development of autoimmune diseases. In adjuvant arthritis, a model for rheumatoid arthritis, we found that the percentage of CD4⁺ T cells expressing the activation marker CD134 (OX40 antigen) was elevated before disease onset. Moreover, these CD134⁺ T cells showed a specific proliferative response to the disease-associated epitope of mycobacterial heat shock protein 60, indicating that this subset contains auto-aggressive T cells. We studied the usefulness of CD134 as a molecular target for immune intervention in arthritis by using liposomes coated with a CD134-directed monoclonal antibody as a drug targeting system. Injection of anti-CD134 liposomes subcutaneously in the hind paws of pre-arthritic rats resulted in targeting of the majority of CD4⁺CD134⁺ T cells in the popliteal lymph nodes. Furthermore, we showed that anti-CD134 liposomes bound to activated T cells were not internalized. However, drug delivery by these liposomes could be established by loading anti-CD134 liposomes with the dipalmitate-derivatized cytostatic agent 5'-fluorodeoxyuridine. These liposomes specifically inhibited the proliferation of activated CD134⁺ T cells in vitro, and treatment with anti-CD134 liposomes containing 5'-fluorodeoxyuridine resulted in the amelioration of adjuvant arthritis. Thus, CD134 can be used as a marker for auto-aggressive CD4⁺ T cells early in arthritis, and specific liposomal targeting of drugs to these cells via CD134 can be employed to downregulate disease development.     

Acute effects of intramuscular aponeurotomy on rat gastrocnemius medialis: force transmission, muscle force and sarcomere length

Acute effects of intramuscular aponeurotomy on muscle force and geometry as a function to muscle length were studied in rat m. gastrocnemius medialis (GM). Acutely after aponeurotomy, activation of the muscle at increasing lengths (acute trajectory) showed a spontaneous and progressive but patial tearing of the connective tissue interface between the fibres inserting directly proximally and distally to the location of the section. After this the muscle consisted morphologically of a stable proximal and a distal part (post-aponeurotomy). Post-aponeurotomy mean active sarcomere length within fibres of the proximal part was shown to be unaffected. In contrast, mean sarcomere length within the distal part was reduced substantially after aponeurotomy. However active sarcomeres in the distal part were still attaining higher lengths with increasing muscle lengths (p<0.005), indicating myofascial force transmission through the intact part of the connective tissue interface of the muscle parts. Post-aponeurotomy optimum muscle force was reduced substantially to less than 45% of pre-aponeurotomy values. During the acute trajectory the muscle yielded approximately 20% higher forces than post-aponeurotomy, indicating that myofascial force transmission was related to the area of connective tissue interface. It is concluded that after aponeurotomy of the proximal aponeurosis of rat GM, fibres without direct myotendinous connection to the origin of the muscle are still able to contribute to muscle force. As the magnitude of reduction in muscle force can only be explained partially by the spontaneous rupture of the connective tissue interface between proximal and distal muscle part, other factors causing a decrease of muscle force are present. Clinical implication of acute effects of intramuscular aponeurotomy are discussed.     

Muscular force transmission: a unified, dual or multiple system? A review and some explorative experimental results

Structures contributing to force transmission in muscle are reviewed combining some historical and relatively recently published experimental data. Also, effects of aponeurotomy and tenotomy are reviewed shortly as well as some new experimental results regarding these interventions that reinforce the concept of myofascial force transmission. The review is also illustrated by some new images of single muscle fibres from Xenopus Laevis indicative of such transmission and some data about locations of insertion of human gluteus maximus muscle. From this review and the new material, emerges a line of thought indicating that mechanical connections between muscle fibres and intramuscular connective tissue play an important role in force transmission. New experimental observations are presented for non-spanning muscle (i.c., rat biceps femoris muscle), regarding the great variety of types of intramuscular connections that exist i n addition to myo-tendinous junctions at the perimuscular ends of muscle fibres. Such connections are classified as (1) tapered end connections, (2) Myo-myonal junctions, (3) myo-epimysial junctions and (3) Myo-endomysial junctions. This line of thought is followed up by consideration of a possible role of connections of intra- and extramuscular connective tissue in force transmission out of the muscle. Experimental results of an explorative nature, regarding the interactions of extensor digitorum longus (EDL), tibialis anterior (TA) and hallucis longus (HAL) muscles within a relatively intact dorsal flexor compartment of the rat hind leg, indicate that: (1) length force properties of EDL are influenced by TA activity in a length dependent fashion. Depending on TA length, force exerted by EDL, kept at constant origin insertion distance, is variable and the effect is influenced by EDL length itself as well; (2) Force is transmitted from muscle to extramuscular connective tissue and vice versa. As a consequence force exerted at proximal and distal tendons of a muscle are not always equal. The difference being transmitted by extramuscular connective tissue and may appear at the tendons of other muscles or may be transmitted via connective tissue directly to bone. It is concluded that the system of force transmission from skeletal muscle should be considered as a multiple system.     

Intermuscular interaction via myofascial force transmission: effects of tibialis anterior and extensor hallucis longus length on force transmission from rat extensor digitorum longus muscle.

Force transmission in rat anterior crural compartment, containing tibialis anterior (TA), extensor hallucis longus (EHL) and extensor digitorum longus (EDL) muscles, was investigated. These muscles together with the muscles of the peroneal compartment were excited maximally. Force was measured at both proximal and distal tendons of EDL muscle as well as at the tied distal tendons of TA and EHL muscles (the TA + EHL complex). Effects of TA + EHL complex length and force on proximally and distally measured forces of EDL muscle kept at constant muscle-tendon complex length were assessed. Length changes of EDL muscle were imposed by movement of the proximal force transducer to different positions.Proximal EDL force was unequal to distal EDL force (active as well as passive) over a wide range of EDL muscle-tendon complex lengths. This is an indication that force is also transmitted out of EDL muscle via pathways other than the tendons (i.e. inter- and/or extramuscular myofascial force transmission). At constant low EDL length, distal lengthening of the TA + EHL complex increased proximal EDL force and decreased distal EDL force. At optimum EDL length, TA+EHL active force was linearly related to the difference between proximal and distal EDL active force. These results indicate intermuscular myofascial force transmission between EDL muscle and the TA + EHL complex. The most likely pathway for this transmission is via connections of the intact intermuscular connective tissue network. The length effects of the TA + EHL complex can be understood on the basis of changes in the configuration, and consequently the stiffness, of these connections. Damage to connective tissue of the compartment decreased the proximo-distal EDL force difference, which indicates the importance of an intact connective tissue network for force transmission from muscle fibers to bone.     

Pandinus imperator scorpion venom blocks voltage-gated potassium channels in GH3 cells

We examined the effects of Pandinus imperator scorpion venom on voltage-gated potassium channels in cultured clonal rat anterior pituitary cells (GH3 cells) using the gigohm-seal voltage-clamp method in the whole-cell configuration. We found that Pandinus venom blocks the voltage-gated potassium channels of GH3 cells in a voltage-dependent and dose-dependent manner. Crude venom in concentrations of 50-500 micrograms/ml produced 50-70% block of potassium currents measured at -20 mV, compared with 25-60% block measured at +50 mV. The venom both decreased the peak potassium current and shifted the voltage dependence of potassium current activation to more positive potentials. Pandinus venom affected potassium channel kinetics by slowing channel opening, speeding deactivation slightly, and increasing inactivation rates. Potassium currents in cells exposed to Pandinus venom did not recover control amplitudes or kinetics even after 20-40 min of washing with venom-free solution. The concentration dependence of crude venom block indicates that the toxins it contains are effective in the nanomolar range of concentrations. The effects of Pandinus venom were mimicked by zinc at concentrations less than or equal to 0.2 mM. Block of potassium current by zinc was voltage dependent and resembled Pandinus venom block, except that block by zinc was rapidly reversible. Since zinc is found in crude Pandinus venom, it could be important in the interaction of the venom with the potassium channel. We conclude that Pandinus venom contains toxins that bind tightly to voltage-dependent potassium channels in GH3 cells. Because of its high affinity for voltage-gated potassium channels and its irreversibility, Pandinus venom may be useful in the isolation, mapping, and characterization of voltage-gated potassium channels.     

Architecture of the human gastrocnemius muscle and some functional consequences

Measurements were performed on the m. gastrocnemius of eight human cadavers in order to describe, in some detail, the architecture of the muscle and its heads. The fibres of the lateral head contain more sarcomeres than those of the medial head. The effect of this difference on the length-force curve of the muscle, calculated with a planimetric muscle model, is diminished by the effect of the difference of fibre angle with respect to the line of pull of the muscle. Within the heads some variation of the number of sarcomeres of the proximal and distal fibres occurs in all muscles. In the lateral head the distal fibres contain fewer sarcomeres than the proximal fibres. In the medial head this is also found in some heads, while others show the reverse. In the lateral head the longer fibres have smaller angles of attachment to the tendon plate and vice versa, while in the medial heads this relationship is only found occasionally. Some variation in the number of sarcomeres is found in the fibres of one bundle. The effects of variations in the number of sarcomeres on the length-force curve are probably insignificant at greater muscle lengths, but may have some importance for the individual with relatively small muscle lengths.