Mechanical regulation of myofibroblast phenoconversion and collagen contraction

Activated fibroblasts promote physiological wound repair following tissue injury. However, dysregulation of fibroblast activation contributes to the development of fibrosis by enhanced production and contraction of collagen-rich extracellular matrix. At the peak of their activities, fibroblasts undergo phenotypic conversion into highly contractile myofibroblasts by developing muscle-like features, including formation of contractile actin-myosin bundles. The phenotype and function of fibroblasts and myofibroblasts are mechanically regulated by matrix stiffness using a feedback control system that is integrated with the progress of tissue remodelling. The actomyosin contraction machinery and cell-matrix adhesion receptors are critical elements that are needed for mechanosensing by fibroblasts and the translation of mechanical signals into biological responses. Here, we focus on mechanical and chemical regulation of collagen contraction by fibroblasts and the involvement of these factors in their phenotypic conversion to myofibroblasts.