On the 3D Correlation between Myofibroblast Shape and Contraction

Cell shape is known to correlate closely with stress-fiber geometry and function, and is thus a critical feature of cell biophysical state. However, the relationship between myofibroblast shape and contraction is complex, even as well in regards to steady-state contractile level (basal tonus). At present, the relationship between myofibroblast shape and basal tonus in 3D is poorly understood. Herein, we utilize the aortic valve interstitial cell (AVICs) as a representative myofibroblast to investigate the relationship between basal tonus and overall cell shape. AVICs were embedded within 3D poly (ethylene glycol) (PEG) hydrogels containing degradable peptide crosslinkers, adhesive peptide sequences, and sub-micron fluorescent micro-spheres to track the local displacement field. We then developed a methodology to evaluate the correlation between overall AVIC shape and basal tonus induced contraction. We computed a volume averaged stretch tensor <U> for the volume occupied by the AVIC, which had three distinct eigenvalues (1.08, 0.99, and 0.89), suggesting that AVIC shape is a result of anisotropic contraction. Furthermore, the direction of maximum contraction correlated closely with the longest axis of a bounding ellipsoid enclosing the AVIC. As gel--imbedded AVIC are known to be in a stable state by three days of incubation used herein, this finding suggests that the overall quiescent AVIC shape is driven by the underlying stress-fiber directional structure and possibly contraction level.