Universität zu Köln

Pollmann, Charlotte, Haug, Michael, Reischl, Barbara, Proelss, Gerhard, Poeschel, Thorsten, Rupitsch, Stefan J., Clemen, Christoph S., Schroeder, Rolf and Friedrich, Oliver ORCID: 0000-0003-2238-2049 (2020). Growing Old Too Early: Skeletal Muscle Single Fiber Biomechanics in Ageing R349P Desmin Knock-in Mice Using the MyoRobot Technology. Int. J. Mol. Sci., 21 (15). BASEL: MDPI. ISSN 1422-0067

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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 ourMyoRobotto 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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pollmann, Charlotte UNSPECIFIED UNSPECIFIED UNSPECIFIED Haug, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Reischl, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Proelss, Gerhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Poeschel, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Rupitsch, Stefan J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrich, Oliver UNSPECIFIED orcid.org/0000-0003-2238-2049 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-324882
DOI:	10.3390/ijms21155501
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	21
Number:	15
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VIMENTIN INTERMEDIATE-FILAMENTS; CONTRACTILE PROPERTIES; PASSIVE STIFFNESS; FORCE GENERATION; MUTANT DESMIN; FAST-TWITCH; SLOW; AGE; ADULT; YOUNG Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32488