On Force and Form: Mechano-Biochemical Regulation of Extracellular Matrix

The extracellular matrix is well-known for its structural role in supporting cells and tissues, and its important biochemical role in providing signals to cells has increasingly become apparent. These structural and biochemical roles are closely coupled through mechanical forces: the biochemistry of the extracellular matrix determines its mechanical properties, mechanical forces control release or display of biochemical signals from the extracellular matrix, and the mechanical properties of the matrix in turn influence the mechanical set point at which signals are sent. In this Perspective, we explain how the extracellular matrix is regulated by strain and mechanical forces. We show the impact of biochemistry and mechanical forces on in vivo assembly of extracellular matrix and illustrate how matrix can be generated in vitro using a variety of methods. We cover how the matrix can be characterized in terms of mechanics, composition, and conformation to determine its properties and to predict interactions. Finally, we explore how extracellular matrix remodeling, ligand binding, and hemostasis are regulated by mechanical forces. These recently discovered mechano-biochemical interactions have important functions in wound healing and disease progression. It is likely that mechanically altered extracellular matrix interactions are a commonly recurring theme, but due to limited tools to generate extracellular matrix fibers in vitro and lack of high-throughput methods to detect these interactions, it is hypothesized that many of these interactions have yet to be discovered.