Dystrophin As a Molecular Shock Absorber.
ACS Nano
; 12(12): 12140-12148, 2018 12 26.
Article
en En
| MEDLINE
| ID: mdl-30457830
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 â¼800 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Distrofina
Límite:
Humans
Idioma:
En
Revista:
ACS Nano
Año:
2018
Tipo del documento:
Article