UC San Diego
Ultrastructure Alterations in Pathological Fibrotic Skeletal Muscle of Mice and Humans
- Author(s): Meza, Rachel
- Advisor(s): Lieber, Richard L
- Kristan, William
- et al.
It is considered that excessive extracellular matrix (ECM) content, specifically an increase in collagen concentration, may be causing the disruption of normal muscle mechanics in disorders presenting muscular stiffness. A clinical example is cerebral palsy (CP), caused by a neurological pathology, that results in muscle spasticity, uncontrolled movements, and/or contractures. An example of excess ECM is also known as skeletal muscle fibrosis. Thus we used both cerebral palsy muscles and fibrotic mouse muscles as our models for muscle stiffness. Our aim was to elucidate the collagen environment in stiff muscles compared to control muscles, in order to find a functional relationship to stiffness. Collagen content was quantified via ELISA and was found that all of the four main stiffness collagen isoforms have a 2.46 ± 0.19 fold increase in CP. However, these increases are at ratios proportional to concentrations found in control. Further investigations on the structure of collagen tendrils in a fibrotic environment are currently underway utilizing a new imaging technique referred to as Serial Block Face Scanning Electron Microscopy (SBFSEM), which gives a 3D reconstruction of the ultrastructure. Preliminary data is showing a trend towards an increase in fibroblasts as the cause of the collagen increase in the fibrotic mouse model. More human model samples will have to be tested for further conclusions on collagen packing and fibroblast number. Bearing in mind that muscle function is highly correlated with the ECM network, these findings may suggest that increased stiffness in fibrosis could be due to irregular ECM remodeling.