The Contributions of Extracellular Matrix and Sarcomere Properties to Passive Muscle Stiffness in Cerebral Palsy

Cerebral palsy results from an upper motor neuron lesion and significantly affects skeletal muscle stiffness. The increased stiffness that occurs is partly a result of changes in the microstructural components of muscle. In particular, alterations in extracellular matrix, sarcomere length, fibre diameter, and fat content have been reported; however, experimental studies have shown wide variability in the degree of alteration. Many studies have reported changes in the extracellular matrix, while others have reported no differences. A consistent finding is increased sarcomere length in cerebral palsy affected muscle. Often many components are altered simultaneously, making it difficult to determine the individual effects on muscle stiffness. In this study, we use a three dimensional modelling approach to isolate individual effects of microstructural alterations typically occurring due to cerebral palsy on whole muscle behaviour; in particular, the effects of extracellular matrix volume fraction, stiffness, and sarcomere length. Causation between the changes to the microstructure and the overall muscle response is difficult to determine experimentally, since components of muscle cannot be manipulated individually; however, utilising a modelling approach allows greater control over each factor. We find that extracellular matrix volume fraction has the largest effect on whole muscle stiffness and mitigates effects from sarcomere length.