Matrix Softness Induces an Afibrogenic Lipofibroblast Phenotype in Fibroblasts from Patients with Idiopathic Pulmonary Fibrosis

Abstract

Contractile myofibroblasts immersed in stiffened remodeled extracellular matrix characterize fibrotic lesions in idiopathic pulmonary fibrosis. Lipofibroblasts are lipid droplet–containing interstitial fibroblasts that support functional homeostasis of the developing and adult lung. We show that stiff substrates augment myofibroblast differentiation and extracellular matrix production in vitro under basal conditions and following TGF-b1 (transforming growth factor-b1) incubation when cultured on tissue culture plastic, whereas culture in soft microenvironments (as spheroids or on soft collagen–coated substrate) redirects myofibroblasts to a lipofibroblast-like phenotype (identified by expres..