Here we present data that suggest the importance of substrate stiffness on CF phenotype with increased stiffness promoting cytoskeletal protein production (αSMA and transgelin), increased nuclear translocation of transcriptional activators (YAP and MRTF-A), and decreased expression of transcriptional repressors (PPAR-γ) in normal CFs. This evidence concerns the gene ACTA1 and cystic fibrosis.