Tissue mechanics coevolves with fibrillar matrisomes in healthy and fibrotic tissues

Fibrillar proteins are principal components of extracellular matrix (ECM) that confer mechanical properties to tissues. Fibrosis can result from wound repair in nearly every tissue in adults, and it associates with increased ECM density and crosslinking as well as increased tissue stiffness. Such fibrotic tissues are a major biomedical challenge, and an emerging view posits that the altered mechanical environment supports both synthetic and contractile myofibroblasts in a state of persistent activation. Here, we review the matrisome in several fibrotic diseases, as well as normal tissues, with a focus on physicochemical properties. Stiffness generally increases with the abundance of fibrillar collagens, the major constituent of ECM, with similar mathematical trends for fibrosis as well as adult tissues from soft brain to stiff bone and heart development. Changes in expression of other core matrisome and matrisome-associated proteins or proteoglycans contribute to tissue stiffening in fibrosis by organizing collagen, crosslinking ECM, and facilitating adhesion of myofibroblasts. Understanding how ECM composition and mechanics coevolve during fibrosis can lead to better models and help with antifibrotic therapies.