Quantifying The 3D Mechanical Tractions Of The Aortic Heart Valve Interstitial Cell

Seminar:

Quantifying The 3D Mechanical Tractions Of The Aortic Heart Valve Interstitial Cell
Friday, December 6, 2019
1PM – 2PM
POB 4.304

Alex Khang

The aortic valve interstitial cell (AVIC) is the most abundant cell type within the aortic valve and maintains the turnover of extracellular matrix (ECM) components. Under normal conditions, AVICs display a fibroblast-like, quiescent phenotype and can undergo myofibroblastic phenotypic activation in response to growth and disease which is characterized by an increase in overall cell contractility as well as an increase in ECM production and remodeling. Prolonged activation of AVICs can potentially cause drastic pathological changes in aortic valve ECM, geometry, and mechanical function and manifest into diseases such as aortic valve regurgitation or stenosis.

Cell contraction is a key component in biological processes such as wound-closure and can influence 3D tissue organization, remodeling, and function. Previous attempts to quantify cell contractility have largely relied on two dimensional assays such as traction force microscopy and micro-post assays which do not recapitulate the three dimensional complexity of native tissues. In this presentation, I will discuss our investigation of AVIC contractile behavior within 3D peptide-modified poly (ethylene glycol) (PEG) hydrogel matrices. We perform macro- and micro-level experiments to assess the contractile response of AVICs at the population- and single-cell levels, respectively. At the population-level, our results show that AVIC contraction within the PEG gel environment increases the overall stiffness of the AVIC-hydrogel construct and that AVIC contractile effects are highly dependent upon the adhesive ligand density within the PEG gel. In addition, we observed that the effects of AVIC contraction were more pronounced in lower stiffness hydrogels. At the single cell level, we used 3D traction force microscopy to assess AVIC contractile response and report that AVIC contraction is highly complex displaying contraction in one direction, expansion in an orthogonal direction, and virtually no deformation in the direction orthogonal to the previous two. In conjunction with our experimental investigations, we developed computational models of the macro- and micro-level experiments to gain a better mechanistic understanding of AVIC contractile behaviors. The macro-level model predicted that AVIC contraction causes an increase in AVIC-hydrogel construct stiffness and we observed that the Neo-Hookean material model was a good approximation of macro-level AVIC-hydrogel mechanical response. At the single-cell level, the Neo-Hookean material model is not sufficient to capture the effects of AVIC contraction on the hydrogel material, especially in regions further away from the cell surface. This discrepancy may have implications towards the complex and length-scale dependent AVIC-hydrogel interactions within our 3D culture system. The tunable and efficient techniques we have developed in this body of work will be used to quantify intrinsic differences in contractile properties between normal and diseased human AVICs to better our understanding of disease progression.

Bio
Alex Khang is a PhD candidate in the Department of Biomedical Engineering at The University of Texas at Austin. He received his BS degree in Biomedical Engineering from the University of Arkansas-Fayetteville. His doctoral project is focused on studying the mechanics and mechanobiology of heart valve interstitial cells (VIC) within a highly tunable hydrogel environment. He previously worked under the tutelage of Dr. Kartik Balachandran in the Mechanobiology and Soft Materials Laboratory. Fabricated nanofibrous scaffolds for tissue engineering applications using a novel technique called centrifugal jet spinning.

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