Dystrophin As a Molecular Shock Absorber

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

Research output: Contribution to journalArticle

6 Scopus citations

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

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Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

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