(18d) Cell Shape Regulates Myofibroblast Activation

Myofibroblasts, specialized cells within the body that aid in normal wound healing processes, exert large contractile forces on their microenvironment with the primary job of these cells being to assist in the closure of wounds.  Aberrant and chronic activation of myofibroblasts can lead to the development of pathological conditions including fibrosis and cancer.  Mechanical tension is thought to be crucial for the activation of myofibroblasts from other cell types, however, a mechanistic understanding of how biophysical cues regulate myofibroblast phenotype is not clear.  Here, we employ a microfabrication approach to investigate the role of cellular shape and tension in the development of myofibroblasts.  We find that cell shape controls the subcellular localization of key mechanoresponsive molecules and subsequent expression of cytoskeletal proteins that contribute to the increased contractile features characteristic of activated myofibroblasts.  Results provide insight into how biophysical cues contribute to the development of myofibroblasts and may suggest ways to treat or prevent pathologies including fibrosis and cancer.