Resistance to radial expansion limits muscle strain and work

Abstract

The collagenous extracellular matrix (ECM) of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance. Here we combine a mathematical model and experimental manipulations to examine how changes in the mechanical properties of the ECM constrain the ability of muscle fibers and fascicles to radially expand and how such a constraint may limit active muscle shortening. We model the mechanical interaction between a contracting muscle and the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model shows that as the proportion of a muscle cross section made up of ECM increases, the muscle’s ability to expand radially is compromised, which in turn restricts muscle shortening. In our experiments, we use a physical constraint placed around the muscle to restrict radial expansion during a contraction. Our experimental results are consistent with model predictions and show that muscles restricted from radial expansion undergo less shortening and generate less mechanical work under identical loads and stimulation conditions. This work highlights the intimate mechanical interaction between contractile and connective tissue structures within skeletal muscle and shows how a deviation from a healthy, well-tuned relationship can compromise performance.

Shear strain rate from phase contrast velocity encoded MRI: Application to study effects of aging in the medial gastrocnemius muscle

“…In univariate analysis, several SR parameters were significantly correlated with force, confirming that both normal and shear SRs significantly predict muscle force output. It is also noteworthy that, in multivariable regression, the two significant predictors of force in a cohort of young and senior subjects are SR indices SR cc and SR fc _max ; both are known from other studies to be related to the status of the ECM …”

“…The results of the SR analysis in the principal basis and in the fiber basis show that normal strains along the fiber (SR fiber and SR ff ) and in the fiber cross‐section (SR in‐plane ) are significantly lower in the aging cohort. Azizi et al showed by combining a mathematical model with experimental manipulation that the structural changes in the ECM (eg, increase in collagen and in stiffness) compromise the muscle's ability to expand radially, which in turn restricts muscle shortening . Thus, the observed changes in both normal strains (along the fiber as well as in the fiber cross‐section) can be attributed, at least in part, to the structural changes in the ECM.…”

“…Azizi et al showed by combining a mathematical model with experimental manipulation that the structural changes in the ECM (eg, increase in collagen and in stiffness) compromise the muscle's ability to expand radially, which in turn restricts muscle shortening. 15 Thus, the observed changes in both normal strains (along the fiber as well as in the fiber crosssection) can be attributed, at least in part, to the structural changes in the ECM. Significant differences in the maximum shear SR were found between young and senior cohorts.…”

“…It is also noteworthy that, in multivariable regression, the two significant predictors of force in a cohort of young and senior subjects are SR indices SR cc and SR fc_max ; both are known from other studies to be related to the status of the ECM. [15][16][17] It should be emphasized that the SR is in reality a 333 tensor, whereas only the 2 3 2 SR tensor is computed here. The inability to compute the full 3 3 3 tensor arises from the fact that a single slice is acquired, which, although encoded for velocity in three orthogonal directions, does not allow the computations of the velocity gradient in the slice direction (thus precluding a 3 3 3 tensor analysis).…”

Muscle unloading: A comparison between spaceflight and ground‐based models

“…Independent of changes in collagen content, mechanical unloading also disrupts the normal three‐dimensional arrangement of collagen fibres in the skeletal muscle. In normal orientation, collagen fibres are either running parallel to the muscle fibres preventing over‐elongation and over‐contraction, or run perpendicular to the muscle fibres connecting adjacent muscle fibres in the motor unit . Unloading disturbs this regular orientation of collagen fibres and causes a relative increase in the number of longitudinally and perpendicularly placed collagen fibres, which are likely to hamper force development during muscle contraction.…”