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research-article

MODELING THE FUNCTIONAL ROLE OF VALVE INTERSTITIAL CELL STRESS FIBERS

[+] Author and Article Information
Yusuke Sakamoto

Center for Cardiovascular Simulation Institute for Computational Engineering and Sciences Department of Biomedical Engineering The University of Texas at Austin Austin, Texas 78712
yus.sakamoto@gmail.com

Rachel M. Buchanan

Center for Cardiovascular Simulation Institute for Computational Engineering and Sciences Department of Biomedical Engineering The University of Texas at Austin Austin, Texas 78712
buchanan.rachel11@gmail.com

Johannah S. Adams

Departments of Orthopaedic Surgery and Biomedical Engineering Duke University Medical Center Durham, North Carolina 27710
johannah@gmail.com

Farshid Guilak

Departments of Orthopaedic Surgery, Biomedical Engineering, and Developmental Biology Washington University, St. Louis USA
guilakf@wudosis.wustl.edu

Michael S. Sacks

Center for Cardiovascular Simulation Institute for Computational Engineering and Sciences Department of Biomedical Engineering The University of Texas at Austin Austin, Texas 78712
msacks@ices.utexas.edu

1Corresponding author.

ASME doi:10.1115/1.4035557 History: Received August 12, 2016; Revised December 12, 2016

Abstract

The function of the heart valve interstitial cells (VICs) are intimately connected to heart valve tissue remodeling and repair, as well as initiation of pathological processes. Given the complex three-dimensional VIC structure and associated biomechanical behaviors, we developed a VIC computational continuum mechanics model to determine changes in stress fibers contraction and strain rate sensitivity. Novel experimental data was acquired including stress fiber orientation, expression levels of F-actin and α-SMA, as well as microindentation studies. Measurements were performed using Cytochalasin D, variable KCl molar concentration, and TGF-ß1 (which emulates certain pathological processes) to exlpore how α-SMA and F-actin expression levels influenced stress fiber passive elastic, active contractile, and viscous resistance responses. Unique to this study was the first investigation of strain rate sensitivity in a valve cell. Simulation results indicated that while both F-actin and α-SMA contributed to stress fiber force generation, in the highest activation state the additional incorporation of α-SMA into stress fibers greatly enhanced the force generation due and strain rate sensitivity. Validation of the model was performed by determining the total force that the VIC exerted on the underlying substrate and compared to traction force microscopy studies, which showed good agreement. Results demonstrated that only in VICs with high levels of αSMA expression exhibited significant effect of viscous effects. This is the first step towards understanding how the biomechanical changes in subcellular structure influence the mechanical interaction between VICs and surrounding tissues.

Copyright (c) 2016 by ASME
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