Theoretical predictions of the effects of force transmission by desmin on intersarcomere dynamics

Desmin is an intermediate filament protein in skeletal muscle that forms a meshlike network around Z-disks. A model of a muscle fiber was developed to investigate the mechanical role of desmin. A two-dimensional mesh of viscoelastic sarcomere elements was connected laterally by elastic elements representing desmin. The equations of motion for each sarcomere boundary were evaluated at quasiequilibrium to determine sarcomere stresses and strains. Simulations of passive stretch and fixed-end contractions yielded values for sarcomere misalignment and stress in wild-type and desmin null fibers. Passive sarcomere misalignment increased nonlinearly with fiber strain in both wild-type and desmin null simulations and was significantly larger without desmin. During fixed-end contraction, desmin null simulations also demonstrated greater sarcomere misalignment and reduced stress production compared with wild-type. In simulations with only a fraction of wild-type desmin present, fixed-end stress increased as a function of desmin concentration and this relationship was influenced by the cellular location of the desmin filaments. This model suggests that desmin stabilizes Z-disks and enables greater stress production by providing a mechanical tether between adjacent myofibrils and to the extracellular matrix and that the significance of the tether is a function of its location within the cell.