Inhibition of focal adhesion kinase increases myofibril viscosity in cardiac myocytes

Cytoskeleton (Hoboken). 2020 Sep;77(9):342-350. doi: 10.1002/cm.21632. Epub 2020 Sep 9.


The coordinated generation of mechanical forces by cardiac myocytes is required for proper heart function. Myofibrils are the functional contractile units of force production within individual cardiac myocytes. At the molecular level, myosin motors form cross-bridges with actin filaments and use ATP to convert chemical energy into mechanical forces. The energetic efficiency of the cross-bridge cycle is influenced by the viscous damping of myofibril contraction. The viscoelastic response of myofibrils is an emergent property of their individual mechanical components. Previous studies have implicated titin-actin interactions, cell-ECM adhesion, and microtubules as regulators of the viscoelastic response of myofibrils. Here we probed the viscoelastic response of myofibrils using laser-assisted dissection. As a proof-of-concept, we found actomyosin contractility was required to endow myofibrils with their viscoelastic response, with blebbistatin treatment resulting in decreased myofibril tension and viscous damping. Focal adhesion kinase (FAK) is a key regulator of cell-ECM adhesion, microtubule stability, and myofibril assembly. We found inhibition of FAK signaling altered the viscoelastic properties of myofibrils. Specifically, inhibition of FAK resulted in increased viscous damping of myofibril retraction following laser ablation. This damping was not associated with acute changes in the electrophysiological properties of cardiac myocytes. These results implicate FAK as a regulator of mechanical properties of myofibrils.

Keywords: cardiac myocyte; focal adhesion kinase; laser ablation; myofibril; myosin II; viscoelasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Focal Adhesions / metabolism*
  • Humans
  • Myocytes, Cardiac / metabolism*
  • Myofibrils / metabolism*
  • Viscosity