Matrix biomechanics and dynamics in pulmonary fibrosis

Abstract

The composition and mechanical properties of the extracellular matrix are dramatically altered during the development and progression of pulmonary fibrosis. Recent evidence indicates that these changes in matrix composition and mechanics are not only end-results of fibrotic remodeling, but active participants in driving disease progression. These insights have stimulated interest in identifying the components and physical aspects of the matrix that contribute to cell activation and disease initiation and progression. This review summarizes current knowledge regarding the biomechanics and dynamics of the ECM in mouse models and human IPF, and discusses how matrix mechanical and compositional changes might be non-invasively assessed, therapeutically targeted, and biologically restored to resolve fibrosis.

Figure 1

Summary of ECM biochemical and biomechanical changes that accompany the shift from a homeostatic ECM present in normal adult lung tissue to a fibrosis promoting ECM present in individuals with pulmonary fibrosis. The hematoxylin and eosin stained histological images shown are from control and bleomycin exposed mouse lungs, and emphasize the heterogeneous appearance of fibrotic remodeling often observed in both mouse models and human pulmonary fibrosis.