(175h) Developing an Elastic Dome for the Study of Cell Mechanobiology

Heart valves are passive tissue structures that control blood flow inside the heart unidirectionally through opening and closing movements, exposed to a variety of mechanical stimuli including shear, pressure, tension, and compression during every cardiac cycle. This complex hemodynamic environment surrounding valve leaflets, when abnormal, may lead to valvular heart disease. Valvular pathological conditions form as results of mechanical forces triggering phenotypical transformation in valvular interstitial cells (VICs), the primary cell population in heart valves responsible for physiologic maintenance, synthesis of ECM components, homeostasis, and remodeling. We therefore investigated stretch-induced effects on VIC phenotype, from quiescent to activated, in an elastic dome using a novel microfluidic device. This device is designed to form an elastic dome with applied pressure mimicking physiological stretch from blood transvalvular pressure inducing valve stretch during peak diastole. VICs are cultured on a polydopamine and gelatin-coated polydimethylsiloxane (PDMS) surface until confluence, and later pressure is applied to stretch VIC cultures. In order to demonstrate VIC activation and transformation, stretch-induced cell responses were examined across strains from 0 to 18%, from physiologic to pathological conditions, revealing myofibroblastic morphology and up-regulation of α-smooth muscle actin expression at higher strains. This platform lays the groundwork for investigating stretch-induced valvular degeneration in an elastic dome and the potential to model other biological systems.