Mutation in the Core Structure of Desmin Intermediate Filaments Affects Myoblast Elasticity

Mutation in the Core Structure of Desmin Intermediate Filaments Affects Myoblast Elasticity

Elastic properties of cells are mainly derived from the actin cytoskeleton. However, intermediate filaments are emerging as major contributors to the mechanical properties of cells. Using atomic force microscopy, we studied the elasticity of mouse myoblasts expressing a mutant form of the gene encod...

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Bibliographic Details
Published in:Biophysical journal Vol. 113; no. 3; pp. 627 - 636
Main Authors: Even, Catherine, Abramovici, Gilles, Delort, Florence, Rigato, Anna F., Bailleux, Virginie, de Sousa Moreira, Abel, Vicart, Patrick, Rico, Felix, Batonnet-Pichon, Sabrina, Briki, Fatma
Format: Journal Article
Language:English
Published: United States Elsevier Inc 08-08-2017
Biophysical Society
The Biophysical Society
Subjects:
Actin
Aggregates
Atomic force microscopy
Atomic structure
Cell Biophysics
Cell Line
Cells
Cytoskeleton
Desmin
Desmin - chemistry
Desmin - genetics
Desmin - metabolism
Elastic properties
Elasticity
Filaments
Fluorescence
Fluorescence microscopy
Heat treatment
Humans
Indentation
Intermediate filaments
Intermediate Filaments - metabolism
Life Sciences
Mechanical properties
Microscopy
Modulus of elasticity
Mutation
Myoblasts
Myoblasts - cytology
Myopathy
Protein Aggregates
Protein Domains
Stress concentration
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Summary:Elastic properties of cells are mainly derived from the actin cytoskeleton. However, intermediate filaments are emerging as major contributors to the mechanical properties of cells. Using atomic force microscopy, we studied the elasticity of mouse myoblasts expressing a mutant form of the gene encoding for desmin intermediate filaments, p.D399Y. This variant produces desmin aggregates, the main pathological symptom of myofibrillar myopathies. Here we show that desmin-mutated cells display a 39% increased median elastic modulus compared to wild-type cells. Desmin-mutated cells required higher forces than wild-type cells to reach high indentation depths, where desmin intermediate filaments are typically located. In addition, heat-shock treatment increased the proportion of cells with aggregates and induced a secondary peak in the distribution of Young’s moduli. By performing atomic force microscopy mechanical mapping combined with fluorescence microscopy, we show that higher Young’s moduli were measured where desmin aggregates were located, indicating that desmin aggregates are rigid. Therefore, we provide evidence that p.D399Y stiffens mouse myoblasts. Based on these results, we suggest that p.D399Y-related myofibrillar myopathy is at least partly due to altered mechanical properties at the single-cell scale, which are propagated to the tissue scale.
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PMCID: PMC5549644
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2017.06.020