Desmin integrates the three-dimensional mechanical properties of muscles

Striated muscle is a linear motor whose properties have been defined in ter ms of uniaxial structures. The question addressed here is what contribution is made to the properties of this motor by extramyofilament cytoskeletal s tructures that are not aligned in parallel with the myofilaments. This ques tion arose from observations that transverse loads increase muscle force pr oduction in diaphragm but not in the hindlimb muscle, thereby indicating th e presence of structures that couple longitudinal and transverse properties of diaphragmatic muscle. Furthermore, we find that the diaphragms of null mutants for the cytoskeletal protein desmin show 1) significant reductions in coupling between the longitudinal and transverse properties, indicating for the first time a role for a specific protein in integrating the three-d imensional mechanical properties of muscle, 2) significant reductions in th e stiffness and viscoelasticity of muscle, and 3) significant increases in tetanic force production. Thus desmin serves a complex mechanical function in diaphragm muscle by contributing both to passive stiffness and viscoelas ticity and to modulation of active force production in a three-dimensional structural network. Our finding changes the paradigm of force transmission among cells by placing our understanding of the function of the cytoskeleto n in the context of the structural and mechanical complexity of muscles.