Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology

Pollmann, Charlotte and Haug, Michael and Reischl, Barbara and Prölß, Gerhard and Pöschel, Thorsten and Rupitsch, Stefan J and Clemen, Christoph S and Schröder, Rolf and Friedrich, Oliver (2020) Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology. International Journal of Molecular Sciences, 21 (15). p. 5501. ISSN 1422-0067

[img]
Preview
Text
Growing-old-too-early-Skeletal-muscle-single-fiber-biomechanics-in-ageing-r349p-desmin-knockin-mice-using-the-myorobot-technologyInternational-Journal-of-Molecular-Sciences.pdf
Available under License Creative Commons Attribution No Derivatives.

Download (1MB) | Preview
Link to published document: http://doi.org/10.3390/ijms21155501

Abstract

Muscle biomechanics relies on 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 may also serve as memory for muscle repositioning following large strains. Our previous analyses of R349P desmin knock-in mice, an animal model for the human R350P desminopathy, already depicted pre-clinical changes in myofibrillar arrangement and increased fiber bundle stiffness. As the effect of R349P desmin on axial biomechanics in fully differentiated single muscle fibers is unknown, we used our MyoRobot to compare passive visco-elasticity and active contractile biomechanics in single fibers from fast- and slow-twitch muscles from adult to senile mice, hetero- or homozygous for the R349P desmin mutation with wild type littermates. We demonstrate that R349P desmin presence predominantly increased axial stiffness in both muscle types with a pre-aged phenotype over wild type fibers. Axial viscosity and Ca2+-mediated force were largely unaffected. Mutant single fibers showed tendencies towards faster unloaded shortening over wild type fibers. Effects of aging seen in the wild type appeared earlier in the mutant desmin fibers. Our single-fiber experiments, free of extracellular matrix, suggest that compromised muscle biomechanics is not exclusively attributed to fibrosis but also originates from an impaired intermediate filament network.

Item Type: Article
Additional Information: Published by MDPI.
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: Repository Administrator
Date Deposited: 20 Aug 2020 03:20
Last Modified: 19 Oct 2021 00:47
URI: http://eprints.victorchang.edu.au/id/eprint/1020

Actions (login required)

View Item View Item