PT  - JOURNAL ARTICLE
AU  - Nilay Taneja
AU  - Abigail C. Neininger
AU  - Matthew R. Bersi
AU  - W. David Merryman
AU  - Dylan T. Burnette
TI  - Focal adhesion kinase regulates early steps of myofibrillogenesis in cardiomyocytes
AID  - 10.1101/261248
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 261248
4099  - http://biorxiv.org/content/early/2018/02/07/261248.short
4100  - http://biorxiv.org/content/early/2018/02/07/261248.full
AB  - Forces generated by myofibrils within cardiomyocytes must be balanced by adhesion to the substrate and to other cardiomyocytes for proper heart function. Loss of this force balance results in cardiomyopathies that ultimately cause heart failure. How this force balance is first established during the assembly of myofibrils is poorly understood. Using human induced pluripotent stem cell derived cardiomyocytes, we show coupling of focal adhesions to myofibrils during early steps of de novo myofibrillogenesis is essential for myofibril maturation. We also establish a key role for Focal adhesion kinase (FAK), a known regulator of adhesion dynamics in non-muscle cells, in regulating focal adhesion dynamics in cardiomyocytes. Specifically, FAK inhibition increased the stability of vinculin in focal adhesions, allowing greater substrate coupling of assembling myofibrils. Furthermore, this coupling is critical for regulating myofibril tension and viscosity. Taken together, our findings uncover a fundamental mechanism regulating the maturation of myofibrils in human cardiomyocytes.