Skeletal muscle has a complex microstructure. Muscle fibers are separated by sheets of intramuscular connective tissue (IMCT) known as endomysium. Fibers are bundled together into fascicles and in turn separated by sheets perimysium connective tissue. Macroscopic finite element (FE) models of muscle lump the properties of fibers and the IMCT together into one transversely isotropic material. These models do not reflect how muscle microstructure affects macroscopic muscle properties, nor do they provide the ability to predict the microscopic stresses and strains experienced by muscle fibers. Therefore, the current understanding of how microstructure influences macroscopic muscle function is limited. The purpose of this dissertation was to investigate structurefunction relationships at the fiber and fascicle scales. To this end, we developed micromechanical models of muscle to:​ (i) explore the effects of microstructure morphology on macroscopic tissue properties, (ii) predict microscopic strains arising from a given macroscopic deformation, and (Hi) provide insights into muscle structurefunction relationships at the microscopic level. The utility of this modeling approach is demonstrated through three applications that will be presented here.

The first goal of this work was to determine the effects of fiber and fascicle cross-sectional geometry on the macroscopic shear properties of muscle. While at the fiber level cross-sectional geometry is similar across muscles and appears isotropic (no preferred direction is evident in the plane of the cross-section), fascicle-level cross-sectional geometries are clearly anisotropic and vary significantly between muscles. Our current understanding of the effects of these variations is limited. Therefore current FE models assume transversely isotropic properties that are the same for all muscles. We created micromechanical models of the fiber and fascicle arrangements of rabbit rectus femoris and soleus muscles. We found that the fascicle-level macroscopic shear moduli were transversely anisotropic and significantly different between the two muscles. These results suggest that shear properties likely vary substantially across different muscles.

The second goal of this work was to determine the effectiveness of force transmission from intra-fascicularly terminating fibers. Many muscles contain fibers that terminate without inserting into a tendon. Force from these fibers can be transmitted through shear within the endomysium that surrounds fibers or through tension within the endomysium that extends from fibers to the tendon;​ however, it is unclear which pathway dominates in force transmission from terminating fibers. We created micromechanical models in order to evaluate the effectiveness of force transmission through each pathway. The models demonstrated that virtually all muscle fibers are able to transmit nearly all of their peak isometric force laterally through shearing of the endomysium. By contrast, the models predicted only limited force transmission ability through tension.

The third goal of this work was to build micromechanical models to investigate the relationship between the mechanics of the myotendinous junction (MTJ) and the propensity for muscle injury. The MTJ is a common site of injury in skeletal muscles and injury is thought to result from excessive sarcomere strains. Analysis of the models revealed that fiber activation significantly increased peak strains in the fiber. This increase may be a mechanism that leads to the higher likelihood of injury during active lengthening of skeletal muscles. Stiffer endomysium mechanical properties resulted in lower peak strains as compared to more compliant endomysium properties. This result suggests that endomysium may play a role in protecting fibers from injury by mitigating strain nonuniformity.

The models presented here introduce a new framework for relating muscle microstructure to muscle function. We have used these models to predict macroscopic properties, propensity for injury, and force generating capacity in healthy muscles. This framework can be extended to investigate how pathological changes in muscle microstructure affect macroscopic and microscopic muscle properties.