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ABSTRACT

Using single cell mechanobiology studies, we examine how disease-linked mutations propagate to change the contractile dynamics and cellular morphology of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). We micropattern islands of adhesive protein to constraining the spreading and alignment of hiPSC-CM on hydrogel substrates containing fluorescent microbeads as fiducial markers for traction force microscopy (TFM). We vary substrate stiffnesses from physiological to diseased/fibrotic, apply mechanical stretch, and apply inotropes and myotropes to vary contractile output. We assessed multiple mutations edited into the WTC line along with isogenic controls under stressors. Some cell lines carried an endogenously labeled alpha-actinin GFP reporter for enabling visualization of sarcomere structure and dynamics with force output. These studies suggest changes in contractile force generation drive remodeling of structure and function at a cell-intrinsic level via changes in mechanosignaling.

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