Desmin Mutation in the C-Terminal Domain Impairs Traction Force Generation in Myoblasts

The cytoskeleton plays a key role in the ability of cells to both resist mechanical stress and generate force, but the precise involvement of intermediate filaments in these processes remains unclear. We focus here on desmin, a type III intermediate filament, which is specifically expressed in muscl...

Full description

Saved in:
Bibliographic Details
Published in:Biophysical journal 2016-01, Vol.110 (2), p.470-480
Main Authors: Charrier, Elisabeth E., Asnacios, Atef, Milloud, Rachel, De Mets, Richard, Balland, Martial, Delort, Florence, Cardoso, Olivier, Vicart, Patrick, Batonnet-Pichon, Sabrina, Hénon, Sylvie
Format: Article
Language:English
Subjects:
Animals
Biological Physics
Biophysics
Cell Biophysics
Cell Line
Cells
Cytoskeleton
Desmin - genetics
Desmin - metabolism
Mice
Motion
Mutation
Mutation, Missense
Myoblasts - metabolism
Physics
Protein Structure, Tertiary
Stress Fibers - genetics
Stress Fibers - metabolism
Stress, Mechanical
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The cytoskeleton plays a key role in the ability of cells to both resist mechanical stress and generate force, but the precise involvement of intermediate filaments in these processes remains unclear. We focus here on desmin, a type III intermediate filament, which is specifically expressed in muscle cells and serves as a skeletal muscle differentiation marker. By using several complementary experimental techniques, we have investigated the impact of overexpressing desmin and expressing a mutant desmin on the passive and active mechanical properties of C2C12 myoblasts. We first show that the overexpression of wild-type-desmin increases the overall rigidity of the cells, whereas the expression of a mutated E413K desmin does not. This mutation in the desmin gene is one of those leading to desminopathies, a subgroup of myopathies associated with progressive muscular weakness that are characterized by the presence of desmin aggregates and a disorganization of sarcomeres. We show that the expression of this mutant desmin in C2C12 myoblasts induces desmin network disorganization, desmin aggregate formation, and a small decrease in the number and total length of stress fibers. We finally demonstrate that expression of the E413K mutant desmin also alters the traction forces generation of single myoblasts lacking organized sarcomeres.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2015.11.3518