The mechanical memory of lung myofibroblasts

摘要: Fibroblasts differentiate into the highly synthetic and contractile myofibroblast phenotype when exposed to substrates with an elastic modulus corresponding pathologically stiff fibrotic tissue. Cellular responses changes in substrate stiffness are typically analyzed after hours or days, which does not enable monitoring of persistence, a hallmark fibrosis. To determine long-lasting effects on behavior lung fibroblasts, we followed novel approach explanting repeatedly passaging fibroblasts silicone representing various states health. Fibrotic activity was determined by assaying for proliferation, cell contractility, expression α-smooth muscle actin, extracellular matrix active TGFβ1. As predicted, low healthy soft increased increasing stiffness. However, mechanically priming 3 weeks resulted sustained even cells were returned cultures 2 weeks. Such primed retained higher than that had been exclusively cultured substrates, statistically different from continuously passaged surfaces. Inversely, partially protected activation shift substrates. Hence, mechano-sensed information relating physical conditions local cellular environment could permanently induce fibroblasts. This effect has important implications progression persistence aggressive diseases such as idiopathic pulmonary