Study of Morphology and Behavior of Pulmonary Arterial Smooth Muscle Cells on Elastomeric Microposts

摘要

Pulmonary arterial hypertension (PAH) is a disease characterized by pulmonary vascular smooth muscle cell (SMC) hyperplasia and hypertrophy, and aberrantly high pulmonary blood pressure leading to heart failure. The median life expectancy is ~2.8 years from diagnosis without any treatment. While the underlying mechanism of PAH remains largely unclear, previous studies have suggested that PAH is accompanied by an extracellular matrix (ECM) remodeling including ECM glycoprotein, Tenascin-C (TN-C) induction in and around the hypertensive PAs, promoting vascular SMC proliferation, migration and angiogenesis. It is known that biophysical (stiffness) and biochemical properties of ECM can have great impacts on cell morphology and cell behavior across several cell types, including mesenchymal stem cells, endothelial cells and muscle stem cells. Here, we aim to establish the relationship between ECM and SMC behavior, using PDMS pillar substrates with variety of stiffnesses to understand the role of ECM in PAH. To this end, we fabricated poly(dimethylsiloxane) (PDMS) micropost arrays to control the variety of ECM stiffnesses to mimic ECM in vivo. By varying the dimension of the micropost (diameter, height and spacing), we effectively tuned the substrate stiffness to be comparable value with the modulus of pulmonary arterial tissue6. We then studied cellular response on these microposts.