Downsizing the molecular spring of the giant protein titin reveals that skeletal muscle titin determines passive stiffness and drives longitudinal hypertrophy.

ABSTRACT: Titin, the largest protein known, forms an elastic myofilament in the striated muscle sarcomere. To establish titin's contribution to skeletal muscle passive stiffness, relative to that of the extracellular matrix, a mouse model was created in which titin's molecular spring region was shortened by deleting 47 exons, the Ttn^Δ112-158 model. RNA sequencing and super-resolution microscopy predicts a much stiffer titin molecule. Mechanical studies with this novel mouse model support that titin is the main determinant of skeletal muscle passive stiffness. Unexpectedly, the in vivo sarcomere length working range was shifted to shorter lengths in Ttn^Δ112-158 mice, due to a ~ 30% increase in the number of sarcomeres in series (longitudinal hypertrophy). The expec

SUBMITTER: Brynnel A 

PROVIDER: S-EPMC6300359 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature