Focal adhesion kinase activation is necessary for stretch-induced alignment and enhanced differentiation of myogenic precursor cells

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13 Citations (Scopus)

Abstract

Myogenic precursors sense and dynamically respond to mechanical stimulation through complex integrin-mediated mechanotransduction, in which focal adhesion kinase (FAK) is a fundamental intracellular signaling mediator. When skeletal myoblasts are exposed to uniaxial cyclic tensile strain (UCTS), they display uniform alignment and an enhanced rate of differentiation. In this work, we explored the role of FAK activation by using C2C12 myoblasts that were grown on flexible culture plates and exposed to UCTS during the early differentiation phase. After 24 h, the cells oriented perpendicularly to the direction of strain and exhibited an enhanced differentiation profile. Next, the cells were exposed to a strain field that was either kept in the same direction or rotated 90°, in the presence or not of an FAK phosphorylation inhibitor. On reorientation of the strain field by 90°, the cells reassembled their focal adhesions and actin cytoskeleton to regain the perpendicular position with respect to the engaging stress. After blocking the FAK, however, the cells failed to respond to the reoriented strain field and their differentiation was abrogated. Interestingly, when the strain field remained in the same direction, the FAK inhibitor compromised the differentiation, even though there was no evident change in cell orientation. Our data indicate that during exposure to UCTS, the activation of FAK is necessary for the myoblasts to undergo alignment and enhanced differentiation.

Original languageEnglish
JournalTissue Engineering. Part A
Volume24
Issue number7-8
Pages (from-to)631-640
Number of pages10
ISSN1937-3341
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Journal Article
  • C2C12
  • Myogenic differentiation
  • Uniaxial cyclic strain
  • Focal adhesion
  • Focal adhesion kinase
  • Myoblasts

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