Seminars

Abstract: Aortic valve interstitial cells (AVICs) reside within the leaflet tissues of the aortic valve and function to replenish, restore, and remodel extracellular matrix components. AVIC contractility is brought about through the contractile properties of the underlying stress fibers and plays a crucial role in processes such as wound healing and mechanotransduction. Currently, it is technically challenging to directly investigate AVIC contractile behaviors within the dense leaflet tissues. As a result, optically clear poly (ethylene glycol) (PEG) hydrogel matrices have been used to study AVIC contractility through means of 3D traction force microscopy (3DTFM). However, the stiffness of the hydrogel material within the vicinity of the AVIC is difficult to measure directly and is further confounded by the remodeling activity of the AVIC. Ambiguity in the local hydrogel mechanical properties can lead to large errors in computed cellular tractions. Herein, we developed an inverse computational approach to estimate AVIC induced remodeling of the hydrogel material. The capabilities of the model were validated with a ground truth data set generated via a test problem comprised of an experimentally measured AVIC geometry and a prescribed modulus field containing unmodified, stiffened, and degraded regions. The inverse model was able to estimate the ground truth data set with high accuracy. When applied to AVICs assessed via 3DTFM, the model estimated regions of significant stiffening and degradation local to the AVIC. We observed that stiffening was largely localized at AVIC protrusions and was likely a result of collagen deposition as confirmed by immunostaining for collagen type 1. Degradation was more spatially uniform and present in regions further away from the AVIC surface and likely a result of enzymatic activity. Our results indicate that AVICs substantially modify the local hydrogel mechanics, which were successfully quantified by our computational model. Looking forward, the established approach will allow for more accurate computation of AVIC contractile force levels and lead to elucidation of stress fiber properties.

Biosketch: Professor Sacks is a world authority on cardiovascular modeling and simulation, particularly on developing patient-specific, simulation-based approaches for the understanding and treatment of heart and heart valve diseases. Dr. Sacks was technical editor of the Journal of Biomechanical Engineering, an inaugural fellow of the Biomedical Engineering Society, a fellow of the American Society of Mechanical Engineers, and a fellow of the American Institute for Medical and Biological Engineering. He has received several awards, including the 2009 Van C. Mow Medal from the ASME Bioengineering Division, the 2008 Chancellor’s Distinguished Research Award of the University of Pittsburgh, the 2008 Richard Skalak Distinguished Lectureship from Columbia University, and the 2008 SKT Lectureship from the City College of New York. In December 2006, Sacks was selected as one of the “Scientific American” 50 leaders in science and technology.