Growing old too early, automated assessment of skeletal muscle single fiber biomechanics in ageing R349P desmin knock-in mice using the MyoRobot technology

Muscle biomechanics is determined by active motor-protein assembly and passive strain transmission through cytoskeletal structures. The desmin filament network aligns myofibrils at the z-discs, provides nuclear-sarcolemmal anchorage and serves as structural muscle memory. Previous analyses of our R3...

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Bibliographic Details
Published inbioRxiv
Main Authors Meyer, Charlotte, Haug, Michael, Reischl, Barbara, Prölß, Gerhard, Pöschel, Thorsten, Rupitsch, Stefan, Clemen, Christoph S, Schröder, Rolf, Friedrich, Oliver
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.08.2019
Subjects
Aging
Biomechanics
Calcium
Cytoskeleton
Desmin
Fibrosis
Genotypes
Myofibrils
Phenotypes
Skeletal muscle
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Summary:Muscle biomechanics is determined by active motor-protein assembly and passive strain transmission through cytoskeletal structures. The desmin filament network aligns myofibrils at the z-discs, provides nuclear-sarcolemmal anchorage and serves as structural muscle memory. Previous analyses of our R349P desmin knock-in mouse model depicted pre-clinical changes in myofibrillar arrangement and increased fiber bundle stiffness. Since the effect of R349P desmin on axial biomechanics in muscle fibers is unknown, we used our MyoRobot to study biomechanics changes in single fibers during aging and across genotypes. We demonstrate that R349P desmin increases axial stiffness in fast- and slow-twitch muscle fibers and promotes a pre-aged phenotype. No systematic changes in Ca2+-mediated force were found. Mutant fibers showed faster unloaded shortening kinetics. Effects of ageing seen in the wild-type appeared earlier in mutant desmin fibers. Impaired R349P desmin muscle biomechanics is clearly an effect of a compromised intermediate filament network rather than secondary to fibrosis.
DOI:10.1101/737973