Effect of desmin knockout on skeletal muscle extracellular matrix organization

Abstract

The genetic deletion of desmin, an intermediate filament in skeletal muscle, leads to lower muscle stress production, muscle stiffness, and fibrosis. The extracellular matrix (ECM) of desmin knockout muscle was studied to determine how its structure and organization change in fibrotic muscle. The abundance and organization of perimysial collagen was quantified by stereological analysis of transmission electron micrographs, and perimysial collagen structure was observed by scanning electron microscopy and confocal imaging of fiber bundles stained for type I collagen. The organization of perimysial collagen termination on muscle fibers was determined by serial block face imaging (3View, Gatan, Inc.). An endomysial mesh was identified, as well as perimysium arranged in large bundles of collagen fibrils. These perimysial “cables” were ~1μm in diameter and tortuous at resting length, but straightened in response to muscle elongation. The apparent load bearing differences of endomysium and perimysium seem to be based on structure, and this structural specialization has not previously been appreciated. Increased stiffness observed in desmin‐null muscle may be partially due to altered ECM organization or material properties in addition to a generalized increase in ECM quantity. Supported by Allergan, Inc. and NIH grants R24 HD05083 and R01 AR057393.