Dystrophin As a Molecular Shock Absorber

Shimin Le, Miao Yu, Ladislav Hovan, Zhihai Zhao, James M Ervasti, Jie Yan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Dystrophin is the largest protein isoform (427 kDa) expressed from the gene defective in Duchenne muscular dystrophy, a lethal muscle-wasting and genetically inherited disease. Dystrophin, localized within a cytoplasmic lattice termed costameres, connects the intracellular cytoskeleton of a myofiber through the cell membrane (sarcolemma) to the surrounding extracellular matrix. In spite of its mechanical regulation roles in stabilizing the sarcolemma during muscle contraction, the underlying molecular mechanism is still elusive. Here, we systematically investigated the mechanical stability and kinetics of the force-bearing central domain of human dystrophin that contains 24 spectrin repeats using magnetic tweezers. We show that the stochastic unfolding and refolding of central domain of dystrophin is able to keep the forces below 25 pN over a significant length change up to ∼800 nm in physiological level of pulling speeds. These results suggest that dystrophin may serve as a molecular shock absorber that defines the physiological level of force in the dystrophin-mediated force-transmission pathway during muscle contraction/stretch, thereby stabilizing the sarcolemma.

Original languageEnglish (US)
Pages (from-to)12140-12148
Number of pages9
JournalACS nano
Volume12
Issue number12
DOIs
StatePublished - Dec 26 2018

Fingerprint

shock absorbers
Shock absorbers
Dystrophin
Muscle
muscular function
Bearings (structural)
Mechanical stability
Cell membranes
Costameres
pulling
Genes
muscles
genes
Proteins
Spectrin
Kinetics
proteins
Protein Isoforms
kinetics
matrices

Keywords

  • dystrophin
  • magnetic tweezers
  • mechanical stability
  • molecular shock absorber
  • sarcolemma

Cite this

Le, S., Yu, M., Hovan, L., Zhao, Z., Ervasti, J. M., & Yan, J. (2018). Dystrophin As a Molecular Shock Absorber. ACS nano, 12(12), 12140-12148. https://doi.org/10.1021/acsnano.8b05721

Dystrophin As a Molecular Shock Absorber. / Le, Shimin; Yu, Miao; Hovan, Ladislav; Zhao, Zhihai; Ervasti, James M; Yan, Jie.

In: ACS nano, Vol. 12, No. 12, 26.12.2018, p. 12140-12148.

Research output: Contribution to journalArticle

Le, S, Yu, M, Hovan, L, Zhao, Z, Ervasti, JM & Yan, J 2018, 'Dystrophin As a Molecular Shock Absorber', ACS nano, vol. 12, no. 12, pp. 12140-12148. https://doi.org/10.1021/acsnano.8b05721
Le S, Yu M, Hovan L, Zhao Z, Ervasti JM, Yan J. Dystrophin As a Molecular Shock Absorber. ACS nano. 2018 Dec 26;12(12):12140-12148. https://doi.org/10.1021/acsnano.8b05721
Le, Shimin ; Yu, Miao ; Hovan, Ladislav ; Zhao, Zhihai ; Ervasti, James M ; Yan, Jie. / Dystrophin As a Molecular Shock Absorber. In: ACS nano. 2018 ; Vol. 12, No. 12. pp. 12140-12148.
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