Central to this process in cardiomyocytes are costameric regions, the region where the sarcolemma connects to the sarcomere, comprised of integrin-talin-vinculin and the dystrophin-glycoprotein complexes (DGC). Biomechanics governs key downstream events (e.g., cytoskeletal rearrangement), directing the overall cellular phenotype in space and time. Finally, we review the current literature to map out how DGC signalling intersects with mechanical signalling pathways to highlight potential future points of intervention, especially with a focus on cardiomyopathies.Ĭells are in continual communication with their microenvironment and the bidirectional dialogue between the two is crucial for the interpretation and integration of biomechanical information. We first discuss the intricate relationship between muscle cell mechanics and function, before examining the recent research for a role of the dystrophin glycoprotein complex in mechanotransduction and maintaining the biomechanical integrity of muscle cells.

This review article aims at providing an up-to-date perspective on the DGC and its role in mechanotransduction. Additionally, evidence is accumulating, linking the DGC to mechanosignalling, albeit this role is still less understood. Dystrophin functions as a molecular spring and the DGC plays a critical role in maintaining the integrity of the sarcolemma. In addition, the loss of a functional DGC leads to progressive dilated cardiomyopathy and premature death. Severing the link between the ECM and the intracellular cytoskeleton has a devastating impact on the homeostasis of skeletal muscle cells, leading to a range of muscular dystrophies. Dystrophin connects the actin cytoskeleton to the extracellular matrix (ECM). Dystrophin is the central protein of the dystrophin-glycoprotein complex (DGC) in skeletal and heart muscle cells.

Protein scaffold of a heart