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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. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/ijms21155501. ISSN 1661-6596.

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Official URL: https://www.mdpi.com/1422-0067/21/15/5501

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 URL in elib:https://elib.dlr.de/135974/
Document Type:Article
Title:Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Pollmann, CharlotteInstitute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen, Bavaria, GermanyUNSPECIFIED
Haug, MichaelInstitute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen, Bavaria, Germanyhttps://orcid.org/0000-0001-5968-2593
Reischl, BarbaraInstitute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen, Bavaria, GermanyUNSPECIFIED
Prölß, GerhardInstitute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen, Bavaria, GermanyUNSPECIFIED
Pöschel, ThorstenInstitute of Multi Scale Simulation of Particulate Systems, Friedrich-Alexander-University Erlangen-Nürnberg, Nägelbachstr. 49b, 91052 Erlangen, Bavaria, GermanyUNSPECIFIED
Rupitsch, Stefan J.Institute of Sensor Technology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3/5, 91052 Erlangen, Bavaria, GermanyUNSPECIFIED
Clemen, Christoph S.Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, GermanyUNSPECIFIED
Schröder, RolfInstitute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Bavaria, GermanyUNSPECIFIED
Friedrich, OliverInstitute of Medical Biotechnology, Friedrich-Alexander-University Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen, Bavaria, Germanyhttps://orcid.org/0000-0003-2238-2049
Date:31 July 2020
Journal or Publication Title:International Journal of Molecular Sciences
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:21
DOI :10.3390/ijms21155501
Page Range:p. 5501
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:1661-6596
Status:Published
Keywords:biomechatronics; desminopathy; R349P desmin; single fibers; skeletal muscle
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Vorhaben Systemphysiologie (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Muscle and Bone Metabolism
Deposited By: Arndt, Carina
Deposited On:08 Sep 2020 13:32
Last Modified:08 Sep 2020 13:32

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