UC San Diego

Proper regulation of the composition and structure of muscle is vital to both its load bearing and force producing capabilities. At every scale of muscular organization, from the individual protein to the whole organ, components communicate with each other to develop and maintain a complex and dynamic equilibrium. The mechanisms and major players involved in this communication are poorly understood. Desmin is an intermediate filament protein integral to the muscle fiber cytoskeleton. It is thought to be involved in stabilizing the contractile apparatus and providing a mechanical link between the cytoskeleton and the extracellular environment. The purpose of this work was to investigate the effects of communication loss caused by desmin deletion on muscle physiology. An approach combining experiments and computational modeling was implemented to show that cytoskeletal alterations in muscle can have wide ranging functional consequences, from gene expression changes in the nucleus to extracellular matrix remodeling