The desmin intermediate filament network in skeletal muscle fibers has been proposed to play a pivotal role in force transmission and maintenance of structural alignment among myofibrils. Fibers from desmin knockout muscles have demonstrated lower isometric stress production and increased sarcomere misalignment in both active and passive deformations. Though it is apparent that desmin filaments affect the mechanical properties of skeletal muscle, the mechanism for such an effect is unclear. To investigate this effect, a mechanical model of a muscle fiber was developed, consisting of a series and parallel connection of viscoelastic sarcomeres. The sarcomeres consist of a force generating element connected to a spring and damper arranged in parallel. The role of desmin was investigated by incorporating the filament as an elastic spring element connecting nodes laterally. Mathematical equations were then developed and solved in quasi-equilibrium, simulating passive stretch and isometric contraction for null and wild type cases. The results show significantly increased sarcomere misalignment for the desmin null case relative to wild type for both isometric contraction and passive stretch. In both cases, both the disparity and the magnitude of misalignment between the cases increase over the duration of the simulations. Additionally, isometric stress production is reduced in the desmin null fibers and the contribution of a given desmin filament to the production of isometric force appears to depend on it’s location within the fiber. These results indicate that the experimentally observed discrepancy in the behavior of desmin null and wild type muscle fibers is likely due to the mechanical link desmin provides between adjacent myofibrils and not to a molecular signaling event or other sarcoplasmic connection. The intermediate filament system is vital for proper muscular function and mutations in these filaments cause debilitating and sometimes fatal diseases. A clear understanding of the functional role of the function of desmin in muscle fibers can aid in therapies that aim to replace this function.
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