Mechanical function of dystrophin in muscle cells

Carmela Pasternak, Scott Wong, Elliot L. Elson

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

Abstract

We have directly measured the contribution of dystrophin to the cortical stiffness of living muscle cells and have demonstrated that lack of dystrophin causes a substantial reduction in stiffness. The inferred molecular structure of dystrophin, its preferential localization underlying the cell surface, and the apparent fragility of muscle cells which lack this protein suggest that dystrophin stabilizes the sarcolemma and protects the myofiber from disruption during contraction. Lacking dystrophin, the muscle cells of persons with Duchenne muscular dystrophy (DMD) are abnormally vulnerable. These facts suggest that muscle cells with dystrophin should be stiffer than similar cells which lack this protein. We have tested this hypothesis by measuring the local stiffness of the membrane skeleton of myotubes cultured from mdx mice and normal controls. Like humans with DMD mdx mice lack dystrophin due to an x-linked mutation and provide a good model for the human disease. Deformability was measured as the resistance to identation of a small area of the cell surface (to a depth of 1 μm) by a glass probe 1 μm in radius. The stiffness of the membrane skeleton was evaluated as the increment of force (mdyne) per μm of indentation. Normal myotubes with an average stiffness value of 1.23 ± 0.04 (SE) mdyne/μm were about fourfold stiffer than myotubes cultured from mdx mice (0.34 ± 0.014 mdyne/μm). We verified by immunofluorescence that both normal and mdx myotubes, which were at a similar developmental stage, expressed sarcomeric myosin, and that dystrophin was detected, diffusely distributed, only in normal, not in mdx myotubes. These results confirm that dystrophin and its associated proteins can reinforce the myotube membrane skeleton by increasing its stiffness and that dystrophin function and, therefore, the efficiency of therapeutic restoration of dystrophin can be assayed through its mechanical effects on muscle cells.

Original languageEnglish
Pages (from-to)355-361
Number of pages7
JournalJournal of Cell Biology
Volume128
Issue number3
DOIs
StatePublished - Feb 1995

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