The contributions of extracellular matrix and sarcomere properties to passive muscle stiffness in cerebral palsy

Abstract

AbstractCerebral palsy results from an upper motor neuron lesion and has significant effects on skeletal muscle stiffness throughout the body. 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 to which each component is altered. Many studies have reported alterations in the extracellular matrix, while others have reported no changes. A consistent finding throughout the literature is increased sarcomere length in cerebral palsy muscle. Often more than one component is altered, making it difficult to determine the individual effects on stiffness. The purpose of this study is to use a modeling approach to isolate individual effects of microstructural alterations that typically occur during cerebral palsy on whole muscle behavior; in particular, the extracellular matrix volume fraction, stiffness, and sarcomere length. These microstructural effects can be captured using a three dimensional model of muscle. We found that the extracellular matrix volume fraction has a larger effect on stiffness compared to sarcomere length, even when coupled with decreased extracellular matrix stiffness. Additionally, the effects of sarcomere length in passive stiffness are mitigated by the increased extracellular matrix volume fraction. Using this model, we can achieve a better understanding of the possible combinations of microstructural changes that can occur during cerebral palsy. Developing these insights into diseased muscle tissue will help to direct future clinical and experimental procedures.