Stretching Skeletal Muscle: Chronic Muscle Lengthening through Sarcomerogenesis

Skeletal muscle responds to passive overstretch through sarcomerogenesis, the creation and serial deposition of new sarcomere units. Sarcomerogenesis is critical to muscle function: It gradually re-positions the muscle back into its optimal operating regime. Animal models of immobilization, limb lengthening, and tendon transfer have provided significant insight into muscle adaptation in vivo. Yet, to date, there is no mathematical model that allows us to predict how skeletal muscle adapts to mechanical stretch in silico. Here we propose a novel mechanistic model for chronic longitudinal muscle growth in response to passive mechanical stretch. We characterize growth through a single scalar-valued internal variable, the serial sarcomere number. Sarcomerogenesis, the evolution of this variable, is driven by the elastic mechanical stretch. To analyze realistic three-dimensional muscle geometries, we embed our model into a nonlinear finite element framework. In a chronic limb lengthening study with a muscle stretch of 1.14, the model predicts an acute sarcomere lengthening from 3.09m to 3.51m, and a chronic gradual return to the initial sarcomere length within two weeks. Compared to the experiment, the acute model error was 0.00% by design of the model; the chronic model error was 2.13%, which lies within the rage of the experimental standard deviation. Our model explains, from a mechanistic point of view, why gradual multi-step muscle lengthening is less invasive than single-step lengthening. It also explains regional variations in sarcomere length, shorter close to and longer away from the muscle-tendon interface. Once calibrated with a richer data set, our model may help surgeons to prevent muscle overstretch and make informed decisions about optimal stretch increments, stretch timing, and stretch amplitudes. We anticipate our study to open new avenues in orthopedic and reconstructive surgery and enhance treatment for patients with ill proportioned limbs, tendon lengthening, tendon transfer, tendon tear, and chronically retracted muscles.     

Muscle and Muscle Fiber Type Transformation In Clawed Crustaceans

SYNOPSIS. The first pair of thoracic limbs in many crustaceansis elaborated into claws in which the principal muscle is thecloser. Changes in the fiber composition of the closer muscleduring claw development, regeneration and reversal are reviewedhere and the hypothesis is advanced that such changes are nerve-dependent.In adult lobsters, Homarus amencanus, the paired claws and closermuscles are bilaterally asymmetric, consisting of a minor orcutter claw with predominantly fast fibers and a small ventralband of slow and a major or crusher claw with 100% slow fibers.Yet in the larval and early juvenile stages the paired clawsand closer muscles are symmetric consisting of a central bandof fast fibers sandwiched by slow. Differentiation into a cutteror crusher muscle during subsequent juvenile development isby appropriate fiber type transformation. Experimental manipulationof the claws or the environment in early juvenile stages whenthe claws are equipotent revealed that the determination ofclaw and closer muscle asymmetry is dependent on the convergenceof neural input from the paired claws: the point of convergencemost likely being the CNS. Bilaterally symmetrical input resultsin the development of paired cutter claws while bilaterallyasymmetric input gives rise to dimorphic, cutter and crusherclaws. In the northern crayfish, Orconectes rusticus, wherethe paired claws are bilaterally similar, the closer muscletransforms its central band of fast fibers to slow, both duringprimary development and regeneration. Whether these fiber typetransformations are nerve-dependent is unknown. In adult snappingshrimps, Alpheus sp., the paired claws and closer muscles areasymmetric: the minor or pincer claw has a central band of fastfibers flanked by slow while the major or snapper claw has 100%slow fibers. Claw reversal occurs with removal of the snapperresulting in the transformation of the existing pincer to asnapper and the regeneration of a new pincer at the old snappersite. Transformation of the closer muscle from pincer to snappertype is by degeneration of the fast fiber band and hypertrophyof the slow fibers. Claw transformation can be either preventedif the pincer nerve is sectioned at the time of snapper removalor promoted if the snapper nerve is sectioned: both resultsimplicating a neural basis for muscle transformation.     

Muscle satellite cells

Skeletal muscle satellite cells are quiescent mononucleated myogenic cells, located between the sarcolemma and basement membrane of terminally-differentiated muscle fibres. These are normally quiescent in adult muscle, but act as a reserve population of cells, able to proliferate in response to injury and give rise to regenerated muscle and to more satellite cells. The recent discovery of a number of markers expressed by satellite cells has provided evidence that satellite cells, which had long been presumed to be a homogeneous population of muscle stem cells, may not be equivalent. It is possible that a sub-population of satellite cells may be derived from a more primitive stem cell. Satellite cell-derived muscle precursor cells may be used to repair and regenerate damaged or myopathic skeletal muscle, or to act as vectors for gene therapy. CELL FACTS: (1) Number of cells in body: 2 x 10(7) to 3 x 10(7) myonuclei/g, 20-25 kg muscle in average man; 2 x 10(5) to 10 x 10(5) satellite cells/g, i.e. approximately 1 x 10(10) to 2 x 10(10) satellite cells per person. (2) Main functions: repair and maintenance of skeletal muscle. (3) Turnover rate: close to zero in non-traumatic conditions-high in disease or severe trauma.