Masters and servants of the force: The role of matrix adhesions in myofibroblast force perception and transmission

Fibroblast-to-myofibroblast differentiation – a key event in the development of fibrocontractive diseases and in wound granulation tissue contraction – is hallmarked by the formation of stress fibers and the neo-expression of α-smooth muscle actin. Incorporation of the smooth muscle actin isoform into stress fibers confers to myofibroblasts a high contractile activity which is transmitted to the extracellular matrix at sites of specialized adhesions, termed ‘fibronexus’ in tissue and ‘supermature focal adhesions’ in two-dimensional cell culture. Myofibroblast differentiation requires a mechanically restrained environment in conjunction with the action of growth factors like transforming growth factor beta and specialized matrix molecules like the ED-A splice variant of fibronectin. This mini-review discusses the roles of myofibroblast adhesions in sensing matrix stress, in transmitting contractile force to the extracellular environment and in creating the high intracellular tension that is required for myofibroblast development.