Stress fiber contractile behaviors in aortic valve interstitial cells

Valve interstitial cells (VICs) are sensitive to their surrounding microenvironments, and excessive and persisting environmental changes cause the improper regulations of VICs, contributing the progression of valve disease. By... [ view full abstract ]

Valve interstitial cells (VICs) are sensitive to their surrounding microenvironments, and excessive and persisting environmental changes cause the improper regulations of VICs, contributing the progression of valve disease. By integrating the microindentation data of the aortic VICs (AVICs) into the model, we studied how the stress fibers in the AVICs adapted to different activation states, and how F-actin and α-SMA each affected the stress fiber biomechanics. The stress fibers were modeled as the ensemble of oriented fibers with passive elastic and active contractile responses; active contraction modeled by length-tension relationship. AVIC data was taken from five experimental groups: Cytochalasin D pretreated group (CytoD), Control groups with 5 mM and 90 mM KCl treatments (C5 and C90 groups, respectively), and transforming growth factor-beta1 (TGF-β1) pretreated groups with 5 mM and 90 mM KCl treatments (T5 and T90 groups, respectively). The contributions of the F-actin and α-SMA from the overall contractile strength of the stress fibers (Figure 1). Treatment with 90 mM KCl and pre-treatment with TGF-β1 activated the AVICs, enhancing the contractile strength of the stress fibers. We found that the incrsase in stress fiber contractile strength directly enhanced the traction force that the AVICs exert on the substrates. While F-actin and α-SMA contributed to be stress fiber force, incorporation of α-SMA had dominant effect on the increase in the stress fiber contractile strength. Thus, in order to understand how the AVICs interact with the surrounding environment, it is critical to model the stress fiber mechanics with the α-SMA component.